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NM_000165.5(GJA1):c.461C>A (p.Thr154Asn) AND Oculodentodigital dysplasia, autosomal recessive

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 24, 2022
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:
RCV003037185.2

Allele description

NM_000165.5(GJA1):c.461C>A (p.Thr154Asn)

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.461C>A (p.Thr154Asn)
HGVS:
  • NC_000006.12:g.121447308C>A
  • NG_008308.1:g.16710C>A
  • NG_109124.1:g.241C>A
  • NM_000165.5:c.461C>AMANE SELECT
  • NP_000156.1:p.Thr154Asn
  • LRG_1289t1:c.461C>A
  • LRG_1289:g.16710C>A
  • LRG_1289p1:p.Thr154Asn
  • NC_000006.11:g.121768454C>A
Protein change:
T154N
Molecular consequence:
  • NM_000165.5:c.461C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Oculodentodigital dysplasia, autosomal recessive
Synonyms:
OCULODENTOOSSEOUS DYSPLASIA, AUTOSOMAL RECESSIVE; ODDD, AUTOSOMAL RECESSIVE; ODOD, AUTOSOMAL RECESSIVE
Identifiers:
MONDO: MONDO:0009768; MedGen: C2749477; Orphanet: 2710; OMIM: 257850

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003439909Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 24, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Oculodentodigital dysplasia with mandibular retrognathism and absence of syndactyly: a case report with a novel mutation in the connexin 43 gene.

van Es RJ, Wittebol-Post D, Beemer FA.

Int J Oral Maxillofac Surg. 2007 Sep;36(9):858-60. Epub 2007 May 16.

PubMed [citation]
PMID:
17509830

GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype.

Paznekas WA, Karczeski B, Vermeer S, Lowry RB, Delatycki M, Laurence F, Koivisto PA, Van Maldergem L, Boyadjiev SA, Bodurtha JN, Jabs EW.

Hum Mutat. 2009 May;30(5):724-33. doi: 10.1002/humu.20958. Review.

PubMed [citation]
PMID:
19338053
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003439909.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Thr154 amino acid residue in GJA1. Other variant(s) that disrupt this residue have been observed in individuals with GJA1-related conditions (PMID: 16813608, 17509830, 19338053, 29927410), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt GJA1 protein function. This missense change has been observed in individuals with clinical features of autosomal dominant oculodentodigital dysplasia (PMID: 16813608; Invitae). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 154 of the GJA1 protein (p.Thr154Asn).

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

Last Updated: Feb 20, 2024