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NM_001110219.3(GJB6):c.680C>T (p.Thr227Met) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 13, 2023
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:
RCV001850643.5

Allele description [Variation Report for NM_001110219.3(GJB6):c.680C>T (p.Thr227Met)]

NM_001110219.3(GJB6):c.680C>T (p.Thr227Met)

Gene:
GJB6:gap junction protein beta 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q12.11
Genomic location:
Preferred name:
NM_001110219.3(GJB6):c.680C>T (p.Thr227Met)
HGVS:
  • NC_000013.11:g.20222801G>A
  • NG_008323.1:g.14595C>T
  • NM_001110219.3:c.680C>TMANE SELECT
  • NM_001110220.3:c.680C>T
  • NM_001110221.3:c.680C>T
  • NM_001370090.1:c.680C>T
  • NM_001370091.1:c.680C>T
  • NM_001370092.1:c.680C>T
  • NM_006783.5:c.680C>T
  • NP_001103689.1:p.Thr227Met
  • NP_001103690.1:p.Thr227Met
  • NP_001103691.1:p.Thr227Met
  • NP_001357019.1:p.Thr227Met
  • NP_001357020.1:p.Thr227Met
  • NP_001357021.1:p.Thr227Met
  • NP_006774.2:p.Thr227Met
  • NP_006774.2:p.Thr227Met
  • LRG_1395t1:c.680C>T
  • LRG_1395:g.14595C>T
  • LRG_1395p1:p.Thr227Met
  • NC_000013.10:g.20796940G>A
  • NM_001110219.2:c.680C>T
  • NM_006783.4:c.680C>T
Protein change:
T227M
Links:
dbSNP: rs199790650
NCBI 1000 Genomes Browser:
rs199790650
Molecular consequence:
  • NM_001110219.3:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001110220.3:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001110221.3:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370090.1:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370091.1:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370092.1:c.680C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006783.5:c.680C>T - 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
Name:
Autosomal recessive nonsyndromic hearing loss 1B
Synonyms:
Deafness, autosomal recessive 1b
Identifiers:
MONDO: MONDO:0012977; MedGen: C2675235; Orphanet: 90636; OMIM: 612645
Name:
Autosomal dominant nonsyndromic hearing loss 3B
Synonyms:
Deafness, autosomal dominant 3b
Identifiers:
MONDO: MONDO:0012975; MedGen: C2675237; Orphanet: 90635; OMIM: 612643
Name:
Hidrotic ectodermal dysplasia syndrome (GJB6)
Synonyms:
CLOUSTON HIDROTIC ECTODERMAL DYSPLASIA; Ectodermal dysplasia 2, hidrotic; Autosomal dominant hidrotic ectodermal dysplasia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007510; MedGen: C0162361; Orphanet: 189; OMIM: 129500; Human Phenotype Ontology: HP:0007529

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002318167Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV002318167.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 227 of the GJB6 protein (p.Thr227Met). This variant is present in population databases (rs199790650, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with GJB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 311379). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GJB6 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024