NM_004004.6(GJB2):c.585G>C (p.Met195Ile) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 1, 2021
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:: RCV001810542.3

Allele description [Variation Report for NM_004004.6(GJB2):c.585G>C (p.Met195Ile)]

NM_004004.6(GJB2):c.585G>C (p.Met195Ile)

Gene:

GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.585G>C (p.Met195Ile)

HGVS:

NC_000013.11:g.20188997C>G
NG_008358.1:g.8979G>C
NM_004004.6:c.585G>CMANE SELECT
NP_003995.2:p.Met195Ile
LRG_1350t1:c.585G>C
LRG_1350:g.8979G>C
LRG_1350p1:p.Met195Ile
NC_000013.10:g.20763136C>G

Protein change:

M195I

Links:

dbSNP: rs570552952

NCBI 1000 Genomes Browser:

rs570552952

Molecular consequence:

NM_004004.6:c.585G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 1A (DFNB1A)
Synonyms:: Deafness nonsyndromic, Connexin 26 linked; Deafness, autosomal recessive 1A; DFNB 1 Nonsyndromic Hearing Loss and Deafness; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009076; MedGen: C2673759; Orphanet: 90636; OMIM: 220290

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002060084	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Uncertain significance (Oct 1, 2021)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22925408, 18941476, 20601923 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002060084

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))

Uncertain significance
(Oct 1, 2021)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Unique spectrum of GJB2 mutations in Mexico.

de la Luz Arenas-Sordo M, Menendez I, Hernández-Zamora E, Sirmaci A, Gutiérrez-Tinajero D, McGetrick M, Murphy-Ruiz P, Leyva-Juárez X, Huesca-Hernández F, Dominguez-Aburto J, Tekin M.

Int J Pediatr Otorhinolaryngol. 2012 Nov;76(11):1678-80. doi: 10.1016/j.ijporl.2012.08.005. Epub 2012 Aug 24.

PubMed [citation]

PMID:: 22925408

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss.

Mani RS, Ganapathy A, Jalvi R, Srikumari Srisailapathy CR, Malhotra V, Chadha S, Agarwal A, Ramesh A, Rangasayee RR, Anand A.

Eur J Hum Genet. 2009 Apr;17(4):502-9. doi: 10.1038/ejhg.2008.179. Epub 2008 Oct 22.

PubMed [citation]

PMID:: 18941476
PMCID:: PMC2986212

See all PubMed Citations (3)

Details of each submission

From Myriad Genetics, Inc., SCV002060084.2

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

Description

NM_004004.5(GJB2):c.585G>C(M195I) is a missense variant classified as a variant of uncertain significance in the context of GJB2-related DFNB1 nonsyndromic hearing loss and deafness. M195I has been observed in cases with relevant disease (PMID: 18941476, 22925408, 20601923). Functional assessments of this variant are not available in the literature. M195I has been observed in population frequency databases (gnomAD: SAS 0.07%). In summary, there is insufficient evidence to classify NM_004004.5(GJB2):c.585G>C(M195I) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.

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

Last Updated: Feb 20, 2024

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