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NM_000070.3(CAPN3):c.1355A>G (p.Asp452Gly) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 3, 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:
RCV003070852.2

Allele description [Variation Report for NM_000070.3(CAPN3):c.1355A>G (p.Asp452Gly)]

NM_000070.3(CAPN3):c.1355A>G (p.Asp452Gly)

Genes:
LOC130056921:ATAC-STARR-seq lymphoblastoid active region 9300 [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.1355A>G (p.Asp452Gly)
HGVS:
  • NC_000015.10:g.42401641A>G
  • NG_008660.1:g.58539A>G
  • NM_000070.2:c.1355A>G
  • NM_000070.3:c.1355A>GMANE SELECT
  • NM_024344.2:c.1355A>G
  • NM_173087.2:c.1211A>G
  • NM_212464.2:c.1094A>G
  • NM_212467.2:c.*1048A>G
  • NP_000061.1:p.Asp452Gly
  • NP_077320.1:p.Asp452Gly
  • NP_775110.1:p.Asp404Gly
  • NP_997629.1:p.Asp365Gly
  • LRG_849t1:c.1355A>G
  • LRG_849:g.58539A>G
  • LRG_849p1:p.Asp452Gly
  • NC_000015.9:g.42693839A>G
Protein change:
D365G
Molecular consequence:
  • NM_000070.3:c.1355A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024344.2:c.1355A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173087.2:c.1211A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_212464.2:c.1094A>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003445636Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Oct 3, 2022)
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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003445636.1

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 452 of the CAPN3 protein (p.Asp452Gly). This variant is present in population databases (rs549092966, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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