NM_033337.3(CAV3):c.377G>A (p.Arg126His) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 7, 2023
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:: RCV000813953.5

Allele description [Variation Report for NM_033337.3(CAV3):c.377G>A (p.Arg126His)]

NM_033337.3(CAV3):c.377G>A (p.Arg126His)

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.377G>A (p.Arg126His)

HGVS:

NC_000003.12:g.8745788G>A
NG_008797.2:g.16979G>A
NM_001234.5:c.377G>A
NM_033337.3:c.377G>AMANE SELECT
NP_001225.1:p.Arg126His
NP_203123.1:p.Arg126His
NP_203123.1:p.Arg126His
LRG_329t1:c.377G>A
LRG_329:g.16979G>A
LRG_329p1:p.Arg126His
NC_000003.11:g.8787474G>A
NM_033337.2:c.377G>A
P56539:p.Arg126His
p.(Arg126His)

Protein change:

R126H

Links:

Leiden Muscular Dystrophy (CAV3): CAV3_00021; UniProtKB: P56539#VAR_029545; dbSNP: rs116840777

NCBI 1000 Genomes Browser:

rs116840777

Molecular consequence:

NM_001234.5:c.377G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033337.3:c.377G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

no known functional consequence

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000954340	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11251997, 29970176, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000954340

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 7, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the caveolin-3 gene: When are they pathogenic?

de Paula F, Vainzof M, Bernardino AL, McNally E, Kunkel LM, Zatz M.

Am J Med Genet. 2001 Apr 1;99(4):303-7.

PubMed [citation]

PMID:: 11251997

Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients.

Fichna JP, Macias A, Piechota M, Korostyński M, Potulska-Chromik A, Redowicz MJ, Zekanowski C.

Hum Genomics. 2018 Jul 3;12(1):34. doi: 10.1186/s40246-018-0167-1.

PubMed [citation]

PMID:: 29970176
PMCID:: PMC6029161

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000954340.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 126 of the CAV3 protein (p.Arg126His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (LGMD) (PMID: 11251997, 29970176). This variant is also known as R125H. ClinVar contains an entry for this variant (Variation ID: 31713). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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