NM_000070.3(CAPN3):c.664G>C (p.Gly222Arg) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 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:: RCV003858778.2

Allele description [Variation Report for NM_000070.3(CAPN3):c.664G>C (p.Gly222Arg)]

NM_000070.3(CAPN3):c.664G>C (p.Gly222Arg)

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.664G>C (p.Gly222Arg)

HGVS:

NC_000015.10:g.42388959G>C
NG_008660.1:g.45857G>C
NM_000070.3:c.664G>CMANE SELECT
NM_024344.2:c.664G>C
NM_173087.2:c.664G>C
NM_212464.2:c.403G>C
NM_212467.2:c.*357G>C
NP_000061.1:p.Gly222Arg
NP_077320.1:p.Gly222Arg
NP_775110.1:p.Gly222Arg
NP_997629.1:p.Gly135Arg
LRG_849t1:c.664G>C
LRG_849:g.45857G>C
LRG_849p1:p.Gly222Arg
NC_000015.9:g.42681157G>C

Protein change:

G135R

Molecular consequence:

NM_000070.3:c.664G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.664G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.664G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_212464.2:c.403G>C - 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

Recent activity

Clear Turn Off Turn On

LOW protein: ATP-dependent RNA helicase-like protein [Arabidopsis thaliana]
LOW protein: ATP-dependent RNA helicase-like protein [Arabidopsis thaliana]
gi|18394218|ref|NP_563968.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004695341	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9762961, 16542520, 22006685, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004695341

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 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

Limb-girdle muscular dystrophy in Guipúzcoa (Basque Country, Spain).

Urtasun M, Sáenz A, Roudaut C, Poza JJ, Urtizberea JA, Cobo AM, Richard I, García Bragado F, Leturcq F, Kaplan JC, Martí Massó JF, Beckmann JS, López de Munain A.

Brain. 1998 Sep;121 ( Pt 9):1735-47.

PubMed [citation]

PMID:: 9762961

Early onset calpainopathy with normal non-functional calpain 3 level.

Lanzillo R, Aurino S, Fanin M, Aguennoz M, Vitale F, Fiorillo C, Del Giudice E, Nigro V, Santoro L.

Dev Med Child Neurol. 2006 Apr;48(4):304-6.

PubMed [citation]

PMID:: 16542520

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004695341.1

#	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. 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. A different variant (c.664G>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 9762961, 16542520, 22006685). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 222 of the CAPN3 protein (p.Gly222Arg).

#	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

ClinVar

Relating variation to medicine