U.S. flag

An official website of the United States government

NM_000070.3(CAPN3):c.692T>C (p.Phe231Ser) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 25, 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:
RCV002025598.6

Allele description [Variation Report for NM_000070.3(CAPN3):c.692T>C (p.Phe231Ser)]

NM_000070.3(CAPN3):c.692T>C (p.Phe231Ser)

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.692T>C (p.Phe231Ser)
HGVS:
  • NC_000015.10:g.42388987T>C
  • NG_008660.1:g.45885T>C
  • NM_000070.3:c.692T>CMANE SELECT
  • NM_024344.2:c.692T>C
  • NM_173087.2:c.692T>C
  • NP_000061.1:p.Phe231Ser
  • NP_077320.1:p.Phe231Ser
  • NP_775110.1:p.Phe231Ser
  • LRG_849t1:c.692T>C
  • LRG_849:g.45885T>C
  • LRG_849p1:p.Phe231Ser
  • NC_000015.9:g.42681185T>C
Protein change:
F231S
Links:
dbSNP: rs1054458336
NCBI 1000 Genomes Browser:
rs1054458336
Molecular consequence:
  • NM_000070.3:c.692T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024344.2:c.692T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173087.2:c.692T>C - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002293626Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 25, 2022) 		germlineclinical testing

PubMed (2)
[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

Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy.

Winckler PB, da Silva AMS, Coimbra-Neto AR, Carvalho E, Cavalcanti EBU, Sobreira CFR, Marrone CD, Machado-Costa MC, Carvalho AAS, Feio RHF, Rodrigues CL, Gonçalves MVM, Tenório RB, Mendonça RH, Cotta A, Paim JFO, Costa E Silva C, de Aquino Cruz C, Bená MI, Betancur DFA, El Husny AS, de Souza ICN, et al.

Clin Genet. 2019 Oct;96(4):341-353. doi: 10.1111/cge.13597. Epub 2019 Jul 15.

PubMed [citation]
PMID:
31268554

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, SCV002293626.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1503640). This missense change has been observed in individual(s) with features of autosomal recessive limb-girdle muscular dystrophy (PMID: 31268554). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 231 of the CAPN3 protein (p.Phe231Ser).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024