NM_000070.3(CAPN3):c.287A>G (p.Gln96Arg) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 7, 2021
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:: RCV002040566.6

Allele description [Variation Report for NM_000070.3(CAPN3):c.287A>G (p.Gln96Arg)]

NM_000070.3(CAPN3):c.287A>G (p.Gln96Arg)

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.287A>G (p.Gln96Arg)

HGVS:

NC_000015.10:g.42360092A>G
NG_008660.1:g.16990A>G
NM_000070.3:c.287A>GMANE SELECT
NM_024344.2:c.287A>G
NM_173087.2:c.287A>G
NP_000061.1:p.Gln96Arg
NP_077320.1:p.Gln96Arg
NP_775110.1:p.Gln96Arg
LRG_849t1:c.287A>G
LRG_849:g.16990A>G
LRG_849p1:p.Gln96Arg
NC_000015.9:g.42652290A>G

Protein change:

Q96R

Links:

dbSNP: rs2141102905

NCBI 1000 Genomes Browser:

rs2141102905

Molecular consequence:

NM_000070.3:c.287A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.287A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.287A>G - 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

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F-box only 31-B-like [Chlorella sorokiniana]
F-box only 31-B-like [Chlorella sorokiniana]
gi|1359821876|gb|PRW57384.1||gnl|WG G|C2E21_3826

Protein
MGAT5 [Myotis davidii]
MGAT5 [Myotis davidii]
Gene ID:102761898

Gene
CD44 [Mauremys reevesii]
CD44 [Mauremys reevesii]
Gene ID:120404487

Gene
ST3GAL5 [Myotis davidii]
ST3GAL5 [Myotis davidii]
Gene ID:102759471

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002298092	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002298092

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 7, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002298092.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CAPN3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 96 of the CAPN3 protein (p.Gln96Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine.

#	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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