NM_000070.3(CAPN3):c.727_730delinsAT (p.Asp243fs) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 30, 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:: RCV000644986.6

Allele description [Variation Report for NM_000070.3(CAPN3):c.727_730delinsAT (p.Asp243fs)]

NM_000070.3(CAPN3):c.727_730delinsAT (p.Asp243fs)

Gene:

CAPN3:calpain 3 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

15q15.1

Genomic location:

Preferred name:

NM_000070.3(CAPN3):c.727_730delinsAT (p.Asp243fs)

HGVS:

NC_000015.10:g.42389022_42389025delinsAT
NG_008660.1:g.45920_45923delinsAT
NM_000070.3:c.727_730delinsATMANE SELECT
NM_024344.2:c.727_730delinsAT
NM_173087.2:c.727_730delinsAT
NP_000061.1:p.Asp243fs
NP_077320.1:p.Asp243fs
NP_775110.1:p.Asp243fs
LRG_849t1:c.727_730delinsAT
LRG_849:g.45920_45923delinsAT
LRG_849p1:p.Asp243fs
NC_000015.9:g.42681220_42681223delinsAT
NM_000070.3:c.727_730delinsAT

Protein change:

D243fs

Links:

dbSNP: rs1555420642

NCBI 1000 Genomes Browser:

rs1555420642

Molecular consequence:

NM_000070.3:c.727_730delinsAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024344.2:c.727_730delinsAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_173087.2:c.727_730delinsAT - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000766720	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10330340, 15689361, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000766720

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 30, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000766720.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change creates a premature translational stop signal (p.Asp243Ilefs*3) 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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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