NM_020631.6(PLEKHG5):c.307G>T (p.Val103Leu) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: May 3, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000705136.1

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.307G>T (p.Val103Leu)]

NM_020631.6(PLEKHG5):c.307G>T (p.Val103Leu)

Gene:
PLEKHG5:pleckstrin homology and RhoGEF domain containing G5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.31
Genomic location:
Preferred name:
NM_020631.6(PLEKHG5):c.307G>T (p.Val103Leu)
HGVS:
  • NC_000001.11:g.6474583C>A
  • NG_007978.1:g.50427G>T
  • NM_001042663.3:c.418G>T
  • NM_001042664.1:c.307G>T
  • NM_001042665.1:c.307G>T
  • NM_001265592.2:c.418G>T
  • NM_001265593.1:c.514G>T
  • NM_001265594.2:c.307G>T
  • NM_020631.6:c.307G>TMANE SELECT
  • NM_198681.4:c.307G>T
  • NP_001036128.2:p.Val140Leu
  • NP_001036129.1:p.Val103Leu
  • NP_001036130.1:p.Val103Leu
  • NP_001252521.2:p.Val140Leu
  • NP_001252522.1:p.Val172Leu
  • NP_001252523.1:p.Val103Leu
  • NP_065682.2:p.Val103Leu
  • NP_941374.3:p.Val103Leu
  • LRG_262:g.50427G>T
  • NC_000001.10:g.6534643C>A
  • NM_020631.4:c.307G>T
Protein change:
V103L
Links:
dbSNP: rs141032388
NCBI 1000 Genomes Browser:
rs141032388
Molecular consequence:
  • NM_001042663.3:c.418G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042664.1:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042665.1:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265592.2:c.418G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265593.1:c.514G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265594.2:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020631.6:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198681.4:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Distal spinal muscular atrophy, autosomal recessive 4 (DSMA4)
Identifiers:
MONDO: MONDO:0012608; MedGen: C1970211; Orphanet: 206580; OMIM: 611067
Name:
Charcot-Marie-Tooth disease, recessive intermediate c (CMTRIC)
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, RECESSIVE INTERMEDIATE C
Identifiers:
MONDO: MONDO:0014154; MedGen: C3809309; Orphanet: 369867; OMIM: 615376

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000834120Invitaecriteria provided, single submitter
Uncertain significance
(May 3, 2018)
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, SCV000834120.1

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

Description

This sequence change replaces valine with leucine at codon 103 of the PLEKHG5 protein (p.Val103Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PLEKHG5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: Nov 27, 2021

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