NM_004086.3(COCH):c.260G>C (p.Gly87Ala) AND Rare genetic deafness

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 13, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000605898.5

Allele description [Variation Report for NM_004086.3(COCH):c.260G>C (p.Gly87Ala)]

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

Genes:

COCH:cochlin [Gene - OMIM - HGNC]
LOC100506071:uncharacterized LOC100506071 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

14q12

Genomic location:

Preferred name:

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

HGVS:

NC_000014.9:g.30878831G>C
NG_008211.2:g.9297G>C
NM_001135058.2:c.260G>C
NM_001347720.2:c.455G>C
NM_004086.3:c.260G>CMANE SELECT
NP_001128530.1:p.Gly87Ala
NP_001334649.1:p.Gly152Ala
NP_004077.1:p.Gly87Ala
NC_000014.8:g.31348037G>C
NM_004086.2:c.260G>C

Protein change:

G152A

Links:

dbSNP: rs1555310861

NCBI 1000 Genomes Browser:

rs1555310861

Molecular consequence:

NM_001135058.2:c.260G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001347720.2:c.455G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004086.3:c.260G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000731610	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Sep 13, 2019)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 23993205, 16835921, 23767834, 26351166, 25230692, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000731610

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Sep 13, 2019)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	3	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical characterization of a novel COCH mutation G87V in a Chinese DFNA9 family.

Chen DY, Chai YC, Yang T, Wu H.

Int J Pediatr Otorhinolaryngol. 2013 Oct;77(10):1711-5. doi: 10.1016/j.ijporl.2013.07.031. Epub 2013 Aug 9.

PubMed [citation]

PMID:: 23993205

Identification of a novel COCH mutation, G87W, causing autosomal dominant hearing impairment (DFNA9).

Collin RW, Pauw RJ, Schoots J, Huygen PL, Hoefsloot LH, Cremers CW, Kremer H.

Am J Med Genet A. 2006 Aug 15;140(16):1791-4. No abstract available.

PubMed [citation]

PMID:: 16835921

See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000731610.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (6)

Description

The p.Gly87Ala variant in COCH has been reported in one individual with adult-onset autosomal dominant hearing loss and segregated in two affected relatives. It has not been identified in large population studies. Glycine (Gly) at position 87 is highly conserved in mammals and evolutionarily distant species, raising the possibility that a change at this position may not be tolerated. Furthermore, two different variants at the same amino acid position (p.Gly87Val and p.Gly87Trp) have been previously reported to segregate with hearing loss in 3 families manifesting autosomal dominant sensorineural hearing loss and vestibular dysfunction (Chen 2013, Collin 2006, Yang 2013). It is located in a functional domain enriched with variants identified in hearing loss patients (Bae 2014). In summary, while additional studies are required to establish fully its clinical significance, the p.Gly87Ala variant is likely pathogenic. ACMG/AMP Criteria applied: PM1, PM2, PM5, PP4, PP1.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		3	not provided	1	not provided

Last Updated: Dec 24, 2023

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