G7444A

# **General Information**

| **Position** | **7444** | **Variant** | **m.7444G\>A** | **Locus** | **MT\-CO1** | **Amino\-AcidChange** | **Term514K** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \- | **APOGEE2** | NA | **Pathogenicity** | Reported \[LB] |

"Pathogenicity" status is derived from published literature or predictions from bioinformatics tools. Researchers and clinicians are cautioned that additional data and/or analysis may still be necessary to confirm the pathological significance of these variants. For more information, please see [Mitofam Info](https://mitofam.com/doc/385/).

# **Pedigree Information**

The **m.7444G\>A** variant in MT\-CO1 has been reported in 26 pedigrees. To date, 47 carriers have been reported. Homoplasmy was reported in 46/47 carriers (97\.9%), and 35/47 carriers (74\.5%) were affected. The main clinical manifestations among affected carriers included onset 1y, profound hearing loss, slope audiogram, onset 3y, 107 dB, profound bilateral hearing impairment, profound hearing impairment, PTA 108, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 7444 | m.7444G\>A | G7444A\-F7 | Caucasian | LHON | ND | ND | 1992 | [1322638](https://pubmed.ncbi.nlm.nih.gov/1322638/) |  |
| 2 | 7444 | m.7444G\>A | G7444A\-F8 | Caucasian | LHON | ND | ND | 1992 | [1322638](https://pubmed.ncbi.nlm.nih.gov/1322638/) | Carrying m.3460G\>A |
| 3 | 7444 | m.7444G\>A | [G7444A\-F9 ](https://mitofam.com/doc/913/)| Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | 10 | 10 | 2005 | [16152638](https://pubmed.ncbi.nlm.nih.gov/16152638/) | Carrying m.1555A\>G |
| 4 | 7444 | m.7444G\>A | G7444A\-F10 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | ND | ND | 2006 | [16500624](https://pubmed.ncbi.nlm.nih.gov/16500624/) |  |
| 5 | 7444 | m.7444G\>A | G7444A\-F11 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | ND | ND | 2006 | [16500624](https://pubmed.ncbi.nlm.nih.gov/16500624/) |  |
| 6 | 7444 | m.7444G\>A | G7444A\-F12 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | ND | ND | 2007 | [17659260](https://pubmed.ncbi.nlm.nih.gov/17659260/) |  |
| 7 | 7444 | m.7444G\>A | G7444A\-F13 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | 4 | 2 | 2007 | [17659260](https://pubmed.ncbi.nlm.nih.gov/17659260/) | A1555G coexists |
| 8 | 7444 | m.7444G\>A | G7444A\-F14 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | ND | ND | 2007 | [17659260](https://pubmed.ncbi.nlm.nih.gov/17659260/) | A1555G coexists |
| 9 | 7444 | m.7444G\>A | G7444A\-F15 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | 2 | 3 | 2007 | [17659260](https://pubmed.ncbi.nlm.nih.gov/17659260/) | A1555G coexists |
| 10 | 7444 | m.7444G\>A | G7444A\-F16 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | ND | ND | 2007 | [17659260](https://pubmed.ncbi.nlm.nih.gov/17659260/) | A1555G coexists |
| 11 | 7444 | m.7444G\>A | G7444A\-F17 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | ND | ND | 2007 | [17659260](https://pubmed.ncbi.nlm.nih.gov/17659260/) |  |
| 12 | 7444 | m.7444G\>A | G7444A\-F18 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | ND | ND | 2007 | [17659260](https://pubmed.ncbi.nlm.nih.gov/17659260/) |  |
| 13 | 7444 | m.7444G\>A | G7444A\-F19 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | 8 | 1 | 2007 | [17698030](https://pubmed.ncbi.nlm.nih.gov/17698030/) | C1494T coexists. |
| 14 | 7444 | m.7444G\>A | G7444A\-F20 | Chinese | Aminoglycoside\-induced and nonsyndromic hearing loss | 28 | 5 | 2007 | [17698030](https://pubmed.ncbi.nlm.nih.gov/17698030/) | C1494T coexists. |
| 15 | 7444 | m.7444G\>A | [G7444A\-F21](https://mitofam.com/doc/914/) | Greek | Sensorineural hearing loss | 2 | 0 | 2011 | [21056478](https://pubmed.ncbi.nlm.nih.gov/21056478/) | heterozygous GJB2 c.35delG in three tested members |
| 16 | 7444 | m.7444G\>A | G7444A\-F22 | Polish | Nonsyndromic or aminoglycoside\-induced hearing loss | 7 | 1 | 2011 | [21621438](https://pubmed.ncbi.nlm.nih.gov/21621438/) | G66 |
| 17 | 7444 | m.7444G\>A | G7444A\-F23 | Polish | Nonsyndromic or aminoglycoside\-induced hearing loss | 5 | 2 | 2011 | [21621438](https://pubmed.ncbi.nlm.nih.gov/21621438/) | G104; family history affected relatives\=2; A1555G coexists |
| 18 | 7444 | m.7444G\>A | G7444A\-F24 | Polish | Nonsyndromic or aminoglycoside\-induced hearing loss | ND | ND | 2011 | [21621438](https://pubmed.ncbi.nlm.nih.gov/21621438/) | G108 |
| 19 | 7444 | m.7444G\>A | G7444A\-F25 | Polish | Nonsyndromic or aminoglycoside\-induced hearing loss | ND | ND | 2011 | [21621438](https://pubmed.ncbi.nlm.nih.gov/21621438/) | W54B |
| 20 | 7444 | m.7444G\>A | G7444A\-F26 | Chinese | Non\-syndromic hearing loss | ND | ND | 2015 | [25968158](https://pubmed.ncbi.nlm.nih.gov/25968158/) | NS011; family history\=No |
| 21 | 7444 | m.7444G\>A | G7444A\-F27 | Chinese | Non\-syndromic hearing loss | ND | ND | 2015 | [25968158](https://pubmed.ncbi.nlm.nih.gov/25968158/) | LX089; family history\=No |
| 22 | 7444 | m.7444G\>A | G7444A\-F28 | Chinese | Aminoglycoside\-induced/non\-syndromic hearing loss | 2 | 2 | 2015 | [25968158](https://pubmed.ncbi.nlm.nih.gov/25968158/) | MTD063; tRNAAla 5655T\>C coexists |
| 23 | 7444 | m.7444G\>A | G7444A\-F32 | Chinese | Aminoglycoside\-induced/non\-syndromic hearing loss | ND | ND | 2015 | [25968158](https://pubmed.ncbi.nlm.nih.gov/25968158/) | NB148; family history\=Yes |
| 24 | 7444 | m.7444G\>A | G7444A\-F37 | Chinese | Non\-syndromic hearing loss | ND | ND | 2015 | [25968158](https://pubmed.ncbi.nlm.nih.gov/25968158/) | WLT024; homozygous GJB2 235delC coexists |
| 25 | 7444 | m.7444G\>A | G7444A\-F38 | Chinese | Non\-syndromic hearing loss | ND | ND | 2015 | [25968158](https://pubmed.ncbi.nlm.nih.gov/25968158/) | WLT122; homozygous GJB2 235delC and tRNAThr 15942T\>C coexist |
| 26 | 7444 | m.7444G\>A | G7444A\-F41 | Chinese | Non\-syndromic hearing loss | ND | ND | 2020 | [32377700](https://pubmed.ncbi.nlm.nih.gov/32377700/) | Family 1 |

# **Carrier Information**

| **No.** | **Position** | **Variant** | **Family ID** | **Carrier ID** | **Type (Fam/De novo/Uninf)** | **Gender (F/M)** | **Proband (Y/N)** | **Affected (Y/N)** | **Die/Alive(D/A)** | **Age** | **Blood Mutant Level** | **Muscle Mutant level** | **Urine Mutant level** | **Other Mutant level** | **Clinical Features** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 7444 | m.7444G\>A | G7444A\-F7 | G7444A\-F7\-P1 | Fam | ND | Y | Y | ND | ND | Homo | / | / | / | LHON |  |
| 2 | 7444 | m.7444G\>A | G7444A\-F8 | G7444A\-F8\-P2 | Fam | ND | Y | Y | ND | ND | Homo | / | / | / | LHON | Carrying m.3460G\>A |
| 3 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-I\-2 | Uninf | F | N | N | A | 72 | Homo | / | / | / | Normal hearing; PTA 25/26 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 4 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-II\-4 | Fam | F | N | Y | A | 49 | Homo | / | / | / | Moderate hearing impairment; onset 27y; PTA 67/55 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 5 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-II\-6 | Fam | F | N | N | A | 47 | Homo | / | / | / | Normal hearing; PTA 17/10 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 6 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-II\-8 | Fam | F | N | N | A | 44 | Homo | / | / | / | Normal hearing; PTA 15/17 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 7 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-II\-9 | Fam | M | N | Y | A | 41 | Homo | / | / | / | Severe hearing impairment; onset 8y; PTA 90/90 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 8 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-II\-11 | Fam | M | N | Y | A | 41 | Homo | / | / | / | Mild hearing impairment; PTA 28/28 dB | Noise exposure reported; no aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 9 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-II\-13 | Fam | M | N | Y | A | 38 | Homo | / | / | / | Profound hearing impairment; onset 2y; PTA 110/110 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 10 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-II\-14 | Fam | M | N | Y | A | 31 | Homo | / | / | / | Profound hearing impairment; onset 3y; PTA 93/98 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 11 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-3 | Fam | F | Y | Y | A | 26 | Homo | / | / | / | Profound bilateral hearing impairment; onset 1y; PTA 108/97 dB | Proband; gentamicin exposure at age 1; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 12 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-4 | Fam | F | N | Y | A | 21 | Homo | / | / | / | Profound hearing impairment; onset 1y; PTA 100/100 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 13 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-5 | Fam | M | N | Y | A | 19 | Homo | / | / | / | Profound hearing impairment; onset 1y; PTA 105/100 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 14 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-6 | Fam | M | N | Y | A | 17 | Homo | / | / | / | Mild hearing impairment; onset 3y; PTA 27/28 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 15 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-7 | Fam | M | N | Y | A | 24 | Homo | / | / | / | Profound hearing impairment; onset 2y; PTA 87/95 dB | Aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 16 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-8 | Fam | M | N | N | A | 19 | Homo | / | / | / | Normal hearing; PTA 17/20 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 17 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-9 | Fam | F | N | N | A | 21 | Homo | / | / | / | Normal hearing; PTA 15/15 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 18 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-10 | Fam | M | N | N | A | 18 | Homo | / | / | / | Normal hearing; PTA 13/18 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 19 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-11 | Fam | F | N | N | A | 18 | Homo | / | / | / | Normal hearing; PTA 12/5 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 20 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-13 | Fam | F | N | N | A | 19 | Homo | / | / | / | Normal hearing; PTA 0/5 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 21 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-14 | Fam | M | N | N | A | 15 | Homo | / | / | / | Normal hearing; PTA 10/7 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 22 | 7444 | m.7444G\>A | G7444A\-F9 | G7444A\-F9\-III\-15 | Fam | M | N | N | A | 8 | Homo | / | / | / | Normal hearing; PTA 5/10 dB | No aminoglycoside exposure; A1555G coexists; blood homoplasmy reported in matrilineal relatives. |
| 23 | 7444 | m.7444G\>A | G7444A\-F10 | G7444A\-F10\-IV\-1 | Fam | F | Y | Y | A | 11 | Homo | / | / | / | Profound bilateral hearing impairment after gentamicin at age 3; PTA 107/107 dB |  |
| 24 | 7444 | m.7444G\>A | G7444A\-F11 | G7444A\-F11\-III\-1 | Fam | M | Y | Y | A | 15 | Homo | / | / | / | Severe bilateral hearing impairment after streptomycin at age 3; PTA 90/87 dB |  |
| 25 | 7444 | m.7444G\>A | G7444A\-F12 | G7444A\-F12\-IV\-4 | Uninf | F | Y | Y | A | 11 | Homo | / | / | / | Profound bilateral hearing impairment; onset 3y; PTA 107/107 dB; Flat audiogram | Use of aminoglycosides\=Yes; ; blood homoplasmy reported |
| 26 | 7444 | m.7444G\>A | G7444A\-F13 | G7444A\-F13\-III\-1 | Fam | M | Y | Y | A | 15 | Homo | / | / | / | Severe bilateral hearing impairment; onset 3y; PTA 88/87 dB; Flat audiogram | Use of aminoglycosides\=Yes; A1555G coexists; blood homoplasmy reported |
| 27 | 7444 | m.7444G\>A | G7444A\-F14 | G7444A\-F14\-III\-1 | Fam | M | Y | Y | A | 17 | Homo | / | / | / | Profound bilateral hearing impairment; onset \<1y; PTA 102/107 dB; Slope audiogram | Use of aminoglycosides\=Yes; A1555G coexists; blood homoplasmy reported |
| 28 | 7444 | m.7444G\>A | G7444A\-F15 | G7444A\-F15\-IV\-8 | Fam | M | Y | Y | A | 10 | Homo | / | / | / | Profound bilateral hearing impairment; onset \<1y; PTA 102/108 dB; Slope audiogram | Use of aminoglycosides\=Yes; A1555G coexists; blood homoplasmy reported |
| 29 | 7444 | m.7444G\>A | G7444A\-F16 | G7444A\-F16\-III\-4 | Fam | M | Y | Y | A | 12 | Homo | / | / | / | Severe bilateral hearing impairment; onset \<1y; PTA 82/92 dB; Upgrade audiogram | Use of aminoglycosides\=Yes; A1555G coexists; blood homoplasmy reported |
| 30 | 7444 | m.7444G\>A | G7444A\-F17 | G7444A\-F17\-IV\-3 | Fam | M | Y | Y | A | 18 | Homo | / | / | / | Profound bilateral hearing impairment; onset 1y; PTA 108/107 dB; Slope audiogram | Use of aminoglycosides\=Yes; ; blood homoplasmy reported |
| 31 | 7444 | m.7444G\>A | G7444A\-F18 | G7444A\-F18\-IV\-1 | Uninf | F | Y | Y | A | 15 | Homo | / | / | / | Severe bilateral hearing impairment; onset \<1y; PTA 108/90 dB; Upgrade audiogram | Use of aminoglycosides\=Yes; ; blood homoplasmy reported |
| 32 | 7444 | m.7444G\>A | G7444A\-F19 | G7444A\-F19\-III\-1 | Fam | F | Y | Y | A | 2\.5y onset | Homo | / | / | / | Severe bilateral hearing impairment after aminoglycosides; onset 2\.5y; PTA 96/76 dB | C1494T coexists |
| 33 | 7444 | m.7444G\>A | G7444A\-F20 | G7444A\-F20\-IV\-1 | Fam | M | Y | Y | A | 14 | Homo | / | / | / | Severe bilateral hearing impairment after aminoglycosides; onset 3y; PTA 79/96 dB | C1494T coexists |
| 34 | 7444 | m.7444G\>A | G7444A\-F21 | G7444A\-F21\-III2 | Fam | M | Y | Y | A | 13 | Homo | / | / | / | Mild/moderate sensorineural hearing loss; onset 3y; PTA 60/30 dB; speech delay, myopia, attention deficit and hyperactivity | Blood homoplasmy; heterozygous GJB2 c.35delG also present. |
| 35 | 7444 | m.7444G\>A | G7444A\-F21 | G7444A\-F21\-III1 | Fam | M | N | N | A | 15 | Homo | / | / | / | Normal hearing; speech delay reported | Blood homoplasmy; heterozygous GJB2 c.35delG also present. |
| 36 | 7444 | m.7444G\>A | G7444A\-F21 | G7444A\-F21\-II3 | Uninf | F | N | N | A | 36 | Homo | / | / | / | Normal hearing; history of otosclerosis surgery | Blood homoplasmy; heterozygous GJB2 c.35delG also present. |
| 37 | 7444 | m.7444G\>A | G7444A\-F22 | G7444A\-F22\-P1 | Fam | F | Y | Y | A | 8y onset | Homo | / | / | / | Mild/moderate hearing loss; PTA 38/41 dB | Aminoglycoside exposure\=No; ; homoplasmic sequence variant |
| 38 | 7444 | m.7444G\>A | G7444A\-F23 | G7444A\-F23\-P1 | Fam | M | Y | Y | A | 3y onset | Homo | / | / | / | Severe hearing loss; PTA 73/80 dB | Aminoglycoside exposure\=Yes; A1555G coexists; homoplasmic sequence variant |
| 39 | 7444 | m.7444G\>A | G7444A\-F24 | G7444A\-F24\-P1 | Uninf | M | Y | Y | A | 1\.3y onset | Homo | / | / | / | Profound hearing loss; PTA 107/107 dB | Aminoglycoside exposure\=Yes; ; homoplasmic sequence variant |
| 40 | 7444 | m.7444G\>A | G7444A\-F25 | G7444A\-F25\-P1 | Uninf | M | Y | Y | A | 1\.5y onset | Homo | / | / | / | Profound hearing loss; PTA 110/110 dB | Aminoglycoside exposure\=No; ; homoplasmic sequence variant |
| 41 | 7444 | m.7444G\>A | G7444A\-F26 | G7444A\-F26\-III\-2 | Uninf | F | Y | Y | A | 3 | Homo | / | / | / | Profound hearing loss; onset 1y; PTA 113/112 dB; Slope audiogram | Aminoglycoside exposure\=No; ; homoplasmy reported for tRNASer(UCN) variants |
| 42 | 7444 | m.7444G\>A | G7444A\-F27 | G7444A\-F27\-III\-5 | Uninf | M | Y | Y | A | 4 | Homo | / | / | / | Profound hearing loss; onset 1y; PTA 98/105 dB; Slope audiogram | Aminoglycoside exposure\=No; ; homoplasmy reported for tRNASer(UCN) variants |
| 43 | 7444 | m.7444G\>A | G7444A\-F28 | G7444A\-F28\-III\-2 | Fam | F | Y | Y | A | 4 | Homo | / | / | / | Profound hearing loss; onset 1y; PTA 99/102 dB; Slope audiogram | Aminoglycoside exposure\=Yes; tRNAAla 5655T\>C coexists; homoplasmy reported for tRNASer(UCN) variants |
| 44 | 7444 | m.7444G\>A | G7444A\-F32 | G7444A\-F32\-III\-2 | Fam | M | Y | Y | A | 21 | Homo | / | / | / | Profound hearing loss; onset 1y; PTA 115/114 dB; Slope audiogram | Aminoglycoside exposure\=Yes; ; homoplasmy reported for tRNASer(UCN) variants |
| 45 | 7444 | m.7444G\>A | G7444A\-F37 | G7444A\-F37\-III\-2 | Fam | F | Y | Y | A | 13 | Homo | / | / | / | Profound hearing loss; onset 1y; PTA 110/115 dB; Flat audiogram | Aminoglycoside exposure\=No; homozygous GJB2 235delC coexists; homoplasmy reported for tRNASer(UCN) variants |
| 46 | 7444 | m.7444G\>A | G7444A\-F38 | G7444A\-F38\-III\-1 | Fam | F | Y | Y | A | 4 | Homo | / | / | / | Profound hearing loss; onset 2y; PTA 108/108 dB; Slope audiogram | Aminoglycoside exposure\=No; homozygous GJB2 235delC and tRNAThr 15942T\>C coexist; homoplasmy reported for tRNASer(UCN) variants |
| 47 | 7444 | m.7444G\>A | G7444A\-F41 | G7444A\-F41\-III\-12 | Uninf | F | Y | Y | A | 15 | \+ | / | / | / | Profound bilateral hearing loss; onset 10y; PTA 118/110 dB | Aminoglycoside exposure\=No |

For abbreviations and other usage instructions, please see [Mitofam Info](https://mitofam.com/doc/385/).