NM_000070.3(CAPN3):c.2081T>G (p.Leu694Arg) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 11, 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:: RCV001217757.9

Allele description [Variation Report for NM_000070.3(CAPN3):c.2081T>G (p.Leu694Arg)]

NM_000070.3(CAPN3):c.2081T>G (p.Leu694Arg)

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.2081T>G (p.Leu694Arg)

HGVS:

NC_000015.10:g.42409961T>G
NG_008660.1:g.66859T>G
NM_000070.3:c.2081T>GMANE SELECT
NM_024344.2:c.2063T>G
NM_173087.2:c.1805T>G
NM_173088.2:c.545T>G
NM_173089.2:c.86T>G
NM_173090.2:c.86T>G
NP_000061.1:p.Leu694Arg
NP_077320.1:p.Leu688Arg
NP_775110.1:p.Leu602Arg
NP_775111.1:p.Leu182Arg
NP_775112.1:p.Leu29Arg
NP_775113.1:p.Leu29Arg
LRG_849t1:c.2081T>G
LRG_849:g.66859T>G
LRG_849p1:p.Leu694Arg
NC_000015.9:g.42702159T>G
NM_000070.2:c.2081T>G

Protein change:

L182R

Links:

dbSNP: rs1355979542

NCBI 1000 Genomes Browser:

rs1355979542

Molecular consequence:

NM_000070.3:c.2081T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.2063T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.1805T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173088.2:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173089.2:c.86T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173090.2:c.86T>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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internal virion protein [Escherichia phage PE3-1]
internal virion protein [Escherichia phage PE3-1]
gi|645494881|gb|AIB06994.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001389609	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002085548	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jun 20, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001389609

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 11, 2022)

germline

clinical testing

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

SCV002085548

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Jun 20, 2021)

germline

clinical testing

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, SCV001389609.4

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 694 of the CAPN3 protein (p.Leu694Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 946817). 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 disruptive. 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.

#	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

From Natera, Inc., SCV002085548.1

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

#	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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