Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data

Variant: NM_000260.4(MYO7A):c.1183C>T (p.Arg395Cys)

CA6197402

555138 (ClinVar)

Gene: MYO7A
Condition: nonsyndromic genetic deafness
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 55512a59-1ed0-41e4-80d2-be897c90cfe6
Approved on: 2024-09-24
Published on: 2024-09-27

HGVS expressions

NM_000260.4:c.1183C>T
NM_000260.4(MYO7A):c.1183C>T (p.Arg395Cys)
NC_000011.10:g.77160265C>T
CM000673.2:g.77160265C>T
NC_000011.9:g.76871311C>T
CM000673.1:g.76871311C>T
NC_000011.8:g.76548959C>T
NG_009086.1:g.37002C>T
NG_009086.2:g.37020C>T
ENST00000409709.9:c.1183C>T
ENST00000409619.6:c.1150C>T
ENST00000409709.7:c.1183C>T
ENST00000409893.5:c.1183C>T
ENST00000458637.6:c.1183C>T
ENST00000620575.4:c.1183C>T
NM_000260.3:c.1183C>T
NM_001127179.2:c.1183C>T
NM_001127180.1:c.1183C>T
NM_001127180.2:c.1183C>T
NM_001369365.1:c.1150C>T
More

Likely Pathogenic

Met criteria codes 3
PP3 PM3 PP1_Strong
Not Met criteria codes 5
PP4 BA1 PM2 BS1 BP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.1183C>T variant in MYO7A is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 395. The highest population minor allele frequency in gnomAD v4.1 is 0.00008472 (2/23608 alleles) in the South Asian population. (PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.773, which is above the threshold of 0.7, evidence that correlates with impact to MYO7A function (PP3). This variant has been detected in 6 individuals with nonsyndromic genetic hearing loss. Out of 3 of those individuals, 1 was compound heterozygous for the variant and a pathogenic or likely pathogenic variant for Usher syndrome and none of those were confirmed in trans (c.401T>A (p.Ile134Asn), 0 PM3 points, SCV: SCV001232108.5, Invitae). The other 2 were compound heterozygous for the variant and a variant of uncertain significance for nonsyndromic genetic hearing loss, 1 of them was confirmed in trans by family testing (0.25 PM3 points, c.1496T>C (p.Ile499Thr); c.1496T>C(p.Ile499Thr), PMIDs: 34416374, 34979615). 3 individuals were homozygous for the variant (1 PM3 point, PMIDs: 23770805, 27573290, ClinVar SCV: SCV001232108.5, Invitae) (PM3). The variant has been reported to segregate with nonsyndromic genetic hearing loss in 8 affected family members from 3 families (PP1_Strong; PMIDs: 23770805, 27573290, 34979615). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive nonsyndromic genetic hearing loss based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PP1_Strong, PM3, PP3. (ClinGen Hearing Loss VCEP specifications version 2; 7/23/2024)
Met criteria codes
PP3
The computational predictor REVEL gives a score of 0.773, which is above the threshold of 0.7, evidence that correlates with impact to MYO7A function (PP3).
PM3
This variant has been detected in 6 individuals with nonsyndromic genetic hearing loss. Out of 3 of those individuals, 1 was compound heterozygous for the variant and a pathogenic or likely pathogenic variant for Usher syndrome and none of those were confirmed in trans (c.401T>A (p.Ile134Asn), 0 PM3 points, SCV: SCV001232108.5, Invitae). The other 2 were compound heterozygous for the variant and a variant of uncertain significance for nonsyndromic genetic hearing loss, 1 of them was confirmed in trans by family testing (0.25 PM3 points, c.1496T>C (p.Ile499Thr); c.1496T>C(p.Ile499Thr), PMIDs: 34416374, 34979615). 3 individuals were homozygous for the variant (1 PM3 point, PMIDs: 23770805, 27573290, ClinVar SCV: SCV001232108.5, Invitae) (PM3).
PP1_Strong
The variant has been reported to segregate with nonsyndromic genetic hearing loss in 8 affected family members from 3 families (PP1_Strong; PMIDs: 23770805, 27573290, 34979615).
Not Met criteria codes
PP4
No ophthalmologic testing performed on Shahzad family and Naz family was specifically noted to not have RP
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v4.1 is 0.00008472 (2/23608 alleles) in the South Asian population. (PM2_Supporting, BS1, and BA1 are not met).
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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