NM_000070.3(CAPN3):c.2068C>G (p.His690Asp) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 20, 2022
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:: RCV001923564.8

Allele description [Variation Report for NM_000070.3(CAPN3):c.2068C>G (p.His690Asp)]

NM_000070.3(CAPN3):c.2068C>G (p.His690Asp)

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.2068C>G (p.His690Asp)

HGVS:

NC_000015.10:g.42409948C>G
NG_008660.1:g.66846C>G
NM_000070.3:c.2068C>GMANE SELECT
NM_024344.2:c.2050C>G
NM_173087.2:c.1792C>G
NM_173088.2:c.532C>G
NM_173089.2:c.73C>G
NM_173090.2:c.73C>G
NP_000061.1:p.His690Asp
NP_077320.1:p.His684Asp
NP_775110.1:p.His598Asp
NP_775111.1:p.His178Asp
NP_775112.1:p.His25Asp
NP_775113.1:p.His25Asp
LRG_849t1:c.2068C>G
LRG_849:g.66846C>G
LRG_849p1:p.His690Asp
NC_000015.9:g.42702146C>G

Protein change:

H178D

Links:

dbSNP: rs2141222124

NCBI 1000 Genomes Browser:

rs2141222124

Molecular consequence:

NM_000070.3:c.2068C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.2050C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.1792C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173088.2:c.532C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173089.2:c.73C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173090.2:c.73C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002190028	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 20, 2022)	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

SCV002190028

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 20, 2022)

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, SCV002190028.4

#	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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 690 of the CAPN3 protein (p.His690Asp).

#	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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