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_004086.3(COCH):c.260G>C (p.Gly87Ala)

CA389344544

517362 (ClinVar)

Gene: COCH (HGNC:1690)

Condition: nonsyndromic genetic deafness (MONDO:0019497)

Inheritance Mode: Autosomal dominant inheritance

UUID: b17ae703-89d3-413b-b547-8e1701d4e055

Approved on: 2026-09-16

Published on: 2026-09-30

HGVS expressions

NM_004086.3:c.260G>C

NM_004086.3(COCH):c.260G>C (p.Gly87Ala)

NC_000014.9:g.30878831G>C

CM000676.2:g.30878831G>C

NC_000014.8:g.31348037G>C

CM000676.1:g.31348037G>C

NC_000014.7:g.30417788G>C

NG_008211.2:g.9297G>C

ENST00000216361.9:c.455G>C

ENST00000396618.9:c.260G>C

ENST00000555117.2:c.260G>C

ENST00000643575.1:c.260G>C

ENST00000643697.1:n.505G>C

ENST00000644874.2:c.260G>C

ENST00000216361.8:c.260G>C

ENST00000396618.7:c.260G>C

ENST00000460581.6:c.-77G>C

ENST00000475087.5:c.260G>C

ENST00000553772.5:c.239+1103G>C

ENST00000553833.5:n.414G>C

ENST00000555881.5:c.83-1621G>C

ENST00000556908.5:c.212G>C

ENST00000557065.1:c.156-592G>C

NM_001135058.1:c.260G>C

NM_004086.2:c.260G>C

NR_038356.1:n.1618-2279C>G

NM_001347720.1:c.455G>C

NM_001135058.2:c.260G>C

NM_001347720.2:c.455G>C

Likely Pathogenic

PM5_Strong PP4 PP1 PP3 PM2_Supporting

PS4

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 2.0

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The variant NM_004086.3:c.260G>C in COCH is a missense variant predicted to cause substitution of Glycine to Alanine at amino acid 87 (p.Gly87Ala). This variant was not found in gnomAD v4.1.1 (PM2_Supporting met). The in silico predictor REVEL yields a score of 0.793 (PP3 met). This variant was identified in a family (Laboratory for Molecular Medicine internal data, SCV000731610.2), in which it segregated with autosomal dominant, progressive, late-onset HL and concomitant vestibular dysfunction in two affected family members (PP1 met). Given the highly specific phenotype of autosomal dominant, progressive HL with vestibular dysfunction, the HL-VCEP decided to apply PP4 evidence criteria. Two different missense variant c.259G>T (p.Gly87Trp) and c.260G>T (p.Gly87Val) at the same amino acid position have been classified Likely-Pathogenic by the ClinGen HL-VCEP (PM5_Strong met). In summary, based on the current evidence (PM5_Strong, PP1, PP4, PP3 & PM2_Supporting), the variant NM_004086.3(COCH):c.260G>C (p.Gly87Ala) is classified as likely pathogenic for autosomal dominant non-syndromic SNHL based on the ACMG/AMP criteria applied, as specified by the ClinGen HL-VCEP (ClinGen Hearing Loss VCEP specifications version 2; 09/16/2026).

PM5_Strong

Two different missense variant c.259G>T (p.Gly87Trp) and c.260G>T (p.Gly87Val) at the same amino acid position have been classified Likely-Pathogenic by the ClinGen HL-VCEP.

PP4

Given the highly specific phenotype of autosomal dominant, progressive HL with vestibular dysfunction, the HL-VCEP decided to apply PP4 evidence criteria.

PP1

This variant was identified in a family (Laboratory for Molecular Medicine internal data, SCV000731610.2), in which it segregated with autosomal dominant, progressive, late-onset HL and concomitant vestibular dysfunction in two affected family members.

PP3

The in silico predictor REVEL yields a score of 0.793.

PM2_Supporting

This variant was not found in gnomAD v4.1.1.

PS4

This variant was identified in only one family (Laboratory for Molecular Medicine internal data, SCV000731610.2), in which it segregated with autosomal dominant, progressive, late-onset HL and concomitant vestibular dysfunction.

Curation History

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