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NM_000070.3(CAPN3):c.2134C>T (p.Leu712Phe) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 1, 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:
RCV000798205.4

Allele description [Variation Report for NM_000070.3(CAPN3):c.2134C>T (p.Leu712Phe)]

NM_000070.3(CAPN3):c.2134C>T (p.Leu712Phe)

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.2134C>T (p.Leu712Phe)
HGVS:
  • NC_000015.10:g.42410446C>T
  • NG_008660.1:g.67344C>T
  • NM_000070.3:c.2134C>TMANE SELECT
  • NM_024344.2:c.2116C>T
  • NM_173087.2:c.1858C>T
  • NM_173088.2:c.598C>T
  • NM_173089.2:c.139C>T
  • NM_173090.2:c.139C>T
  • NP_000061.1:p.Leu712Phe
  • NP_077320.1:p.Leu706Phe
  • NP_775110.1:p.Leu620Phe
  • NP_775111.1:p.Leu200Phe
  • NP_775112.1:p.Leu47Phe
  • NP_775113.1:p.Leu47Phe
  • LRG_849t1:c.2134C>T
  • LRG_849:g.67344C>T
  • LRG_849p1:p.Leu712Phe
  • NC_000015.9:g.42702644C>T
  • NM_000070.2:c.2134C>T
Protein change:
L200F
Links:
dbSNP: rs794727318
NCBI 1000 Genomes Browser:
rs794727318
Molecular consequence:
  • NM_000070.3:c.2134C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024344.2:c.2116C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173087.2:c.1858C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173088.2:c.598C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173089.2:c.139C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173090.2:c.139C>T - 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
SCV000937807Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 1, 2022) 		germlineclinical testing

PubMed (3)
[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

Limb-girdle muscular dystrophy in the Netherlands: gene defect identified in half the families.

van der Kooi AJ, Frankhuizen WS, Barth PG, Howeler CJ, Padberg GW, Spaans F, Wintzen AR, Wokke JH, van Ommen GJ, de Visser M, Bakker E, Ginjaar HB.

Neurology. 2007 Jun 12;68(24):2125-8.

PubMed [citation]
PMID:
17562833

Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients.

Ten Dam L, Frankhuizen WS, Linssen WHJP, Straathof CS, Niks EH, Faber K, Fock A, Kuks JB, Brusse E, de Coo R, Voermans N, Verrips A, Hoogendijk JE, van der Pol L, Westra D, de Visser M, van der Kooi AJ, Ginjaar I.

Clin Genet. 2019 Aug;96(2):126-133. doi: 10.1111/cge.13544. Epub 2019 May 6.

PubMed [citation]
PMID:
30919934
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000937807.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. 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: 195450). This missense change has been observed in individual(s) with clinical features of autosomal recessive limb-girdle muscular dystrophy (PMID: 17562833, 30919934). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 712 of the CAPN3 protein (p.Leu712Phe).

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

Last Updated: Jul 23, 2024