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NM_000070.3(CAPN3):c.1722del (p.Ser575fs) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 19, 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:
RCV000796843.10

Allele description [Variation Report for NM_000070.3(CAPN3):c.1722del (p.Ser575fs)]

NM_000070.3(CAPN3):c.1722del (p.Ser575fs)

Gene:
CAPN3:calpain 3 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q15.1
Genomic location:
Preferred name:
NM_000070.3(CAPN3):c.1722del (p.Ser575fs)
HGVS:
  • NC_000015.10:g.42402979del
  • NG_008660.1:g.59877del
  • NM_000070.3:c.1722delMANE SELECT
  • NM_024344.2:c.1722del
  • NM_173087.2:c.1578del
  • NM_173088.2:c.186del
  • NP_000061.1:p.Ser575fs
  • NP_077320.1:p.Ser575fs
  • NP_775110.1:p.Ser527fs
  • NP_775111.1:p.Ser63fs
  • LRG_849t1:c.1722del
  • LRG_849:g.59877del
  • LRG_849p1:p.Ser575fs
  • NC_000015.9:g.42695177del
  • NM_000070.2:c.1722del
  • NM_000070.2:c.1722delC
Protein change:
S527fs
Links:
dbSNP: rs1366387924
NCBI 1000 Genomes Browser:
rs1366387924
Molecular consequence:
  • NM_000070.3:c.1722del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_024344.2:c.1722del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_173087.2:c.1578del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_173088.2:c.186del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000936373Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 19, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV000986702GenomeConnect, ClinGen
no classification provided
not providedpaternalphenotyping only

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedpaternalunknownnot providednot providednot providednot providednot providedphenotyping only

Citations

PubMed

Calpainopathy-a survey of mutations and polymorphisms.

Richard I, Roudaut C, Saenz A, Pogue R, Grimbergen JE, Anderson LV, Beley C, Cobo AM, de Diego C, Eymard B, Gallano P, Ginjaar HB, Lasa A, Pollitt C, Topaloglu H, Urtizberea JA, de Visser M, van der Kooi A, Bushby K, Bakker E, Lopez de Munain A, Fardeau M, et al.

Am J Hum Genet. 1999 Jun;64(6):1524-40.

PubMed [citation]
PMID:
10330340
PMCID:
PMC1377896

LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene.

Sáenz A, Leturcq F, Cobo AM, Poza JJ, Ferrer X, Otaegui D, Camaño P, Urtasun M, Vílchez J, Gutiérrez-Rivas E, Emparanza J, Merlini L, Paisán C, Goicoechea M, Blázquez L, Eymard B, Lochmuller H, Walter M, Bonnemann C, Figarella-Branger D, Kaplan JC, Urtizberea JA, et al.

Brain. 2005 Apr;128(Pt 4):732-42. Epub 2005 Feb 2.

PubMed [citation]
PMID:
15689361
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000936373.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Ser575Leufs*20) in the CAPN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with limb-girdle muscular dystrophy type 2A (PMID: 15351423, 25135358). ClinVar contains an entry for this variant (Variation ID: 503683). For these reasons, this variant has been classified as Pathogenic.

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

From GenomeConnect, ClinGen, SCV000986702.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedphenotyping onlynot provided

Description

Variant interpretted as Likely pathogenic and reported on 12/15/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalunknownnot providednot providedvalidationnot providednot providednot providednot provided

Last Updated: Sep 29, 2024