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NM_033337.3(CAV3):c.277G>T (p.Ala93Ser) AND Long QT syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 28, 2018
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:
RCV000687833.2

Allele description [Variation Report for NM_033337.3(CAV3):c.277G>T (p.Ala93Ser)]

NM_033337.3(CAV3):c.277G>T (p.Ala93Ser)

Genes:
CAV3:caveolin 3 [Gene - OMIM - HGNC]
OXTR:oxytocin receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_033337.3(CAV3):c.277G>T (p.Ala93Ser)
Other names:
p.A93S:GCC>TCC
HGVS:
  • NC_000003.12:g.8745688G>T
  • NG_008797.2:g.16879G>T
  • NM_001234.5:c.277G>T
  • NM_033337.3:c.277G>TMANE SELECT
  • NP_001225.1:p.Ala93Ser
  • NP_203123.1:p.Ala93Ser
  • NP_203123.1:p.Ala93Ser
  • LRG_329t1:c.277G>T
  • LRG_329:g.16879G>T
  • LRG_329p1:p.Ala93Ser
  • NC_000003.11:g.8787374G>T
  • NM_033337.2:c.277G>T
Protein change:
A93S
Links:
dbSNP: rs28936686
NCBI 1000 Genomes Browser:
rs28936686
Molecular consequence:
  • NM_001234.5:c.277G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033337.3:c.277G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000815421Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 28, 2018) 		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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000815421.1

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

Description

This sequence change replaces alanine with serine at codon 93 of the CAV3 protein (p.Ala93Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs28936686, ExAC 0.05%). This variant has not been reported in the literature in individuals with CAV3-related disease. ClinVar contains an entry for this variant (Variation ID: 180798). 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 and their clinical significance is uncertain. Variants that disrupt the p.Ala93 amino acid residue in CAV3 have been observed in affected individuals (PMID: 27184587, 12666119, 15668980, 196973670). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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: Jun 23, 2024