NM_000070.3(CAPN3):c.1456C>T (p.Gln486Ter) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 14, 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:: RCV001992920.6

Allele description [Variation Report for NM_000070.3(CAPN3):c.1456C>T (p.Gln486Ter)]

NM_000070.3(CAPN3):c.1456C>T (p.Gln486Ter)

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.1456C>T (p.Gln486Ter)

HGVS:

NC_000015.10:g.42401742C>T
NG_008660.1:g.58640C>T
NM_000070.3:c.1456C>TMANE SELECT
NM_024344.2:c.1456C>T
NM_173087.2:c.1312C>T
NP_000061.1:p.Gln486Ter
NP_077320.1:p.Gln486Ter
NP_775110.1:p.Gln438Ter
LRG_849t1:c.1456C>T
LRG_849:g.58640C>T
LRG_849p1:p.Gln486Ter
NC_000015.9:g.42693940C>T

Protein change:

Q438*

Links:

dbSNP: rs2141199686

NCBI 1000 Genomes Browser:

rs2141199686

Molecular consequence:

NM_000070.3:c.1456C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_024344.2:c.1456C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_173087.2:c.1312C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002230497	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 31268554, 10330340, 15689361, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002230497

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 14, 2023)

germline

clinical testing

PubMed (4)
[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

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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002230497.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1450732). This premature translational stop signal has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 31268554). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln486*) 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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