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NM_000070.3(CAPN3):c.1714C>G (p.Arg572Gly) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 18, 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:
RCV003631134.2

Allele description [Variation Report for NM_000070.3(CAPN3):c.1714C>G (p.Arg572Gly)]

NM_000070.3(CAPN3):c.1714C>G (p.Arg572Gly)

Gene:
CAPN3:calpain 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q15.1
Genomic location:
Preferred name:
NM_000070.3(CAPN3):c.1714C>G (p.Arg572Gly)
HGVS:
  • NC_000015.10:g.42402971C>G
  • NG_008660.1:g.59869C>G
  • NM_000070.3:c.1714C>GMANE SELECT
  • NM_024344.2:c.1714C>G
  • NM_173087.2:c.1570C>G
  • NM_173088.2:c.178C>G
  • NP_000061.1:p.Arg572Gly
  • NP_077320.1:p.Arg572Gly
  • NP_775110.1:p.Arg524Gly
  • NP_775111.1:p.Arg60Gly
  • LRG_849t1:c.1714C>G
  • LRG_849:g.59869C>G
  • LRG_849p1:p.Arg572Gly
  • NC_000015.9:g.42695169C>G
Protein change:
R524G
Links:
dbSNP: rs863224959
NCBI 1000 Genomes Browser:
rs863224959
Molecular consequence:
  • NM_000070.3:c.1714C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024344.2:c.1714C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173087.2:c.1570C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173088.2:c.178C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1)
Synonyms:
Limb-girdle muscular dystrophy, type 2A; Limb-girdle muscular dystrophy type 2; Muscular dystrophy, pelvofemoral; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009675; MedGen: C1869123; Orphanet: 267; OMIM: 253600

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004551720Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 18, 2022) 		germlineclinical testing

PubMed (7)
[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

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.

Nallamilli BRR, Chakravorty S, Kesari A, Tanner A, Ankala A, Schneider T, da Silva C, Beadling R, Alexander JJ, Askree SH, Whitt Z, Bean L, Collins C, Khadilkar S, Gaitonde P, Dastur R, Wicklund M, Mozaffar T, Harms M, Rufibach L, Mittal P, Hegde M.

Ann Clin Transl Neurol. 2018 Dec;5(12):1574-1587. doi: 10.1002/acn3.649.

PubMed [citation]
PMID:
30564623
PMCID:
PMC6292381

Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.

Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C, et al.

Cell. 1995 Apr 7;81(1):27-40.

PubMed [citation]
PMID:
7720071
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004551720.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

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 CAPN3 protein function. ClinVar contains an entry for this variant (Variation ID: 498261). This missense change has been observed in individual(s) with clinical features of limb girdle muscular dystrophy (PMID: 30564623). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 572 of the CAPN3 protein (p.Arg572Gly). This variant disrupts the p.Arg572 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7720071, 10102422, 16650086, 27066545, 27708273). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Sep 29, 2024