Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000260.4(MYO7A):c.2002C>T (p.Arg668Cys)

CA132231

43168 (ClinVar)

Gene: MYO7A (HGNC:4647)

Condition: Usher syndrome (MONDO:0019501)

Inheritance Mode: Autosomal recessive inheritance

UUID: 6a32887c-1612-4a2f-a69d-9c23b9789b97

Approved on: 2026-05-20

Published on: 2026-06-25

HGVS expressions

NM_000260.4(MYO7A):c.2002C>T (p.Arg668Cys)

NM_000260.4:c.2002C>T

NC_000011.10:g.77174822C>T

CM000673.2:g.77174822C>T

NC_000011.9:g.76885868C>T

CM000673.1:g.76885868C>T

NC_000011.8:g.76563516C>T

NG_009086.1:g.51559C>T

NG_009086.2:g.51577C>T

ENST00000409709.9:c.2002C>T

ENST00000409893.6:c.67C>T

ENST00000409619.6:c.1969C>T

ENST00000409709.7:c.2002C>T

ENST00000409893.5:c.2002C>T

ENST00000458637.6:c.2002C>T

ENST00000620575.4:c.2002C>T

NM_000260.3:c.2002C>T

NM_001127179.2:c.2002C>T

NM_001127180.1:c.2002C>T

NM_001127180.2:c.2002C>T

NM_001369365.1:c.1969C>T

Pathogenic

PM3_Very Strong PP3 PP4

PM2

Evidence Links 0

Expert Panel

Hearing Loss VCEP

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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.2002C>T variant in MYO7A is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 668. The highest population minor allele frequency in gnomAD v4.1 is 0.00003344 (48/1179790 alleles) in the European non-finnish population, ( PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.794, which is above the threshold of 0.7, evidence that correlates with impact on MYO7A function (PP3 met). This variant has been detected in 3 individuals with usher syndrome and 1 with sensorineural hearing loss. All of those individuals, were compound heterozygous for the variant and a pathogenic variant and 3 of those were confirmed in trans by parental testing (PM3_VeryStrong, PP4; PMID: 20146813, 26969326, SCV001397007.7, Labcorp Genetics internal data). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PM3_VeryStrong, PP4, PP3. (ClinGen Hearing Loss VCEP specifications version 2; 05/20/2026).

PM3_Very Strong

This variant has been detected in 3 individuals with Usher syndrome and 1 with autosomal recessive nonsyndromic hearing loss. All of those individuals, were compound heterozygous for the variant and a pathogenic variant as confirmed by parental testing

PP3

The computational predictor REVEL gives a score of 0.794, which is above the threshold of 0.7, evidence that correlates with impact on MYO7A function

PP4

This variant has been detected in 3 individuals with Usher syndrome. All of those individuals, were compound heterozygous for the variant and a pathogenic variant as confirmed by parental testing

PM2

The highest population minor allele frequency in gnomAD v4.1 is 0.00003344 (48/1179790 alleles) in the European non-finnish population, (PM2_Supporting not met)

Curation History

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