U.S. flag

An official website of the United States government

NM_000070.3(CAPN3):c.550del (p.Thr184fs) AND Limb-girdle muscular dystrophy, recessive

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 14, 2016
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:
RCV000348995.8

Allele description [Variation Report for NM_000070.3(CAPN3):c.550del (p.Thr184fs)]

NM_000070.3(CAPN3):c.550del (p.Thr184fs)

Gene:
CAPN3:calpain 3 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q15.1
Genomic location:
Preferred name:
NM_000070.3(CAPN3):c.550del (p.Thr184fs)
Other names:
NM_000070.2:c.550del;p.Thr184Argfs*36
HGVS:
  • NC_000015.10:g.42387804del
  • NG_008660.1:g.44702del
  • NM_000070.3:c.550delMANE SELECT
  • NM_000070.3:c.550delA
  • NM_024344.2:c.550del
  • NM_173087.2:c.550del
  • NP_000061.1:p.Thr184fs
  • NP_077320.1:p.Thr184fs
  • NP_077320.1:p.Thr184fs
  • NP_775110.1:p.Thr184fs
  • LRG_849t1:c.550del
  • LRG_849:g.44702del
  • LRG_849p1:p.Thr184fs
  • NC_000015.9:g.42680001del
  • NC_000015.9:g.42680002del
  • NM_000070.2:c.550delA
  • NM_000070.3:c.549delAMANE SELECT
  • NM_000070.3:c.550del
  • NM_000070.3:c.550delAMANE SELECT
  • NM_024344.1:c.550del
  • p.Thr184Argfs*36
  • p.Thr184ArgfsTer36
Protein change:
T184fs
Links:
Genetic Testing Registry (GTR): GTR000330880; OMIM: 114240.0009; dbSNP: rs80338800
NCBI 1000 Genomes Browser:
rs80338800
Molecular consequence:
  • NM_000070.3:c.550del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_024344.2:c.550del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_173087.2:c.550del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Limb-girdle muscular dystrophy, recessive
Identifiers:
MedGen: CN239352

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
SCV000390998Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification 20161018)		Pathogenic
(Jun 14, 2016) 		germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes.

Piluso G, Politano L, Aurino S, Fanin M, Ricci E, Ventriglia VM, Belsito A, Totaro A, Saccone V, Topaloglu H, Nascimbeni AC, Fulizio L, Broccolini A, Canki-Klain N, Comi LI, Nigro G, Angelini C, Nigro V.

J Med Genet. 2005 Sep;42(9):686-93.

PubMed [citation]
PMID:
16141003
PMCID:
PMC1736133

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
See all PubMed Citations (10)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000390998.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

The c.550delA (p.Thr184ArgfsTer36) is a frameshift variant and is predicted to result in premature truncation of the protein. The p.Thr184ArgfsTer36 variant is well reported in the literature. Across a selection of ten studies, the p.Thr184ArgfsTer36 variant is found in over 130 patients with limb-girdle muscular dystrophy 2 including in 54 individuals in a homozygous state, 44 in a compound heterozygous state and ten in a heterozygous state (Richard et al. 1999; Pogoda et al. 2000; Canki-Klain et al. 2004; Piluso et al. 2005; Fanin et al. 2005; Milic et al. 2005; Krahn et al. 2006; Todorova et al. 2007; Chrobáková et al. 2004; Inashkina et al. 2016). The p.Thr184ArgfsTer36 variant was present in a heterozygous state in nine of 1691 healthy controls and is reported at a frequency of 0.005629 in the African American population of the Exome Sequencing Project. Chrobáková et al. (2004) demonstrated an absence of the CAPN3 protein on Western blots for patients who were compound heterozygous for this variant. Based on the collective evidence and the potential impact of frameshift variants, the p.Thr184ArgfsTer36 variant is classified as pathogenic for CAPN3-related disorders.

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

Last Updated: Nov 24, 2024