NM_000166.6(GJB1):c.515C>T (p.Pro172Leu) AND Charcot-Marie-Tooth Neuropathy X

Clinical significance:Pathogenic (Last evaluated: Apr 24, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000559484.1

Allele description [Variation Report for NM_000166.6(GJB1):c.515C>T (p.Pro172Leu)]

NM_000166.6(GJB1):c.515C>T (p.Pro172Leu)

Gene:
GJB1:gap junction protein beta 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq13.1
Genomic location:
Preferred name:
NM_000166.6(GJB1):c.515C>T (p.Pro172Leu)
HGVS:
  • NC_000023.11:g.71224222C>T
  • NG_008357.1:g.14011C>T
  • NM_000166.6:c.515C>TMANE SELECT
  • NM_001097642.3:c.515C>T
  • NP_000157.1:p.Pro172Leu
  • NP_001091111.1:p.Pro172Leu
  • LRG_245t2:c.515C>T
  • LRG_245:g.14011C>T
  • LRG_245p2:p.Pro172Leu
  • NC_000023.10:g.70444072C>T
  • NM_000166.5:c.515C>T
Protein change:
P172L
Links:
dbSNP: rs1555937218
NCBI 1000 Genomes Browser:
rs1555937218
Molecular consequence:
  • NM_000166.6:c.515C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001097642.3:c.515C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth Neuropathy X
Identifiers:
MedGen: CN118851

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000658914Invitaecriteria provided, single submitter
Pathogenic
(Apr 24, 2017)
germlineclinical testing

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

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, SCV000658914.1

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

Description

This sequence change replaces proline with leucine at codon 172 of the GJB1 protein (p.Pro172Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with Charcot-Marie-Tooth disease, type X1 (CMTX1)(PMID: 9856562, 27098783, 21692908). It has also been reported to segregate with disease in a family affected with CMTX1 (PMID: 9633821). This variant is also known as c.577 C>T in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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