U.S. flag

An official website of the United States government

NM_000165.5(GJA1):c.75G>C (p.Trp25Cys) AND Inborn genetic diseases

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 11, 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:
RCV001267462.4

Allele description [Variation Report for NM_000165.5(GJA1):c.75G>C (p.Trp25Cys)]

NM_000165.5(GJA1):c.75G>C (p.Trp25Cys)

Gene:
GJA1:gap junction protein alpha 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q22.31
Genomic location:
Preferred name:
NM_000165.5(GJA1):c.75G>C (p.Trp25Cys)
HGVS:
  • NC_000006.12:g.121446922G>C
  • NG_008308.1:g.16324G>C
  • NM_000165.5:c.75G>CMANE SELECT
  • NP_000156.1:p.Trp25Cys
  • LRG_1289t1:c.75G>C
  • LRG_1289:g.16324G>C
  • LRG_1289p1:p.Trp25Cys
  • NC_000006.11:g.121768068G>C
  • NM_000165.3:c.75G>C
Protein change:
W25C
Links:
dbSNP: rs1773898476
NCBI 1000 Genomes Browser:
rs1773898476
Molecular consequence:
  • NM_000165.5:c.75G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001445643Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jun 11, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

A novel GJA1 mutation in oculodentodigital dysplasia with progressive spastic paraplegia and sensory deficits.

Furuta N, Ikeda M, Hirayanagi K, Fujita Y, Amanuma M, Okamoto K.

Intern Med. 2012;51(1):93-8. Epub 2012 Jan 1.

PubMed [citation]
PMID:
22214631

Missense and deletion mutations in GJA1 causing oculodentodigital dysplasia in two Indian families.

Dwarakanathan A, Bhat M, Gn S, Shetty S.

Clin Dysmorphol. 2015 Oct;24(4):159-62. doi: 10.1097/MCD.0000000000000094. No abstract available.

PubMed [citation]
PMID:
26087145

Details of each submission

From Ambry Genetics, SCV001445643.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.75G>C (p.W25C) alteration is located in exon 2 (coding exon 1) of the GJA1 gene. This alteration results from a G to C substitution at nucleotide position 75, causing the tryptophan (W) at amino acid position 25 to be replaced by a cysteine (C). Based on data from the Genome Aggregation Database (gnomAD), the GJA1 c.75G>C alteration was not observed, with coverage at this position. The p.W25C alteration has been reported in two individuals with oculodentodigital dysplasia. One patient was 34 years old and developed adult-onset progressive spastic paraplegia and sensory deficits in addition to congenital features of ODDD (Furuta, 2012). The other patient had features of ODDD and a normal neurological exam at age 7 years, but white matter changes were seen on brain MRI. Parental testing confirmed his alteration arose de novo (Dwarakanathan, 2015). This amino acid position is highly conserved in available vertebrate species. The p.W25C alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

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

Last Updated: Jun 23, 2024