NM_000070.3(CAPN3):c.2107C>T (p.Leu703Phe) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 10, 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:: RCV001240159.4

Allele description

NM_000070.3(CAPN3):c.2107C>T (p.Leu703Phe)

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.2107C>T (p.Leu703Phe)

HGVS:

NC_000015.10:g.42409987C>T
NG_008660.1:g.66885C>T
NM_000070.3:c.2107C>TMANE SELECT
NM_024344.2:c.2089C>T
NM_173087.2:c.1831C>T
NM_173088.2:c.571C>T
NM_173089.2:c.112C>T
NM_173090.2:c.112C>T
NP_000061.1:p.Leu703Phe
NP_077320.1:p.Leu697Phe
NP_775110.1:p.Leu611Phe
NP_775111.1:p.Leu191Phe
NP_775112.1:p.Leu38Phe
NP_775113.1:p.Leu38Phe
LRG_849t1:c.2107C>T
LRG_849:g.66885C>T
LRG_849p1:p.Leu703Phe
NC_000015.9:g.42702185C>T
NC_000015.9:g.42702185C>T
NM_000070.2:c.2107C>T

Protein change:

L191F

Links:

dbSNP: rs751443759

NCBI 1000 Genomes Browser:

rs751443759

Molecular consequence:

NM_000070.3:c.2107C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.2089C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.1831C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173088.2:c.571C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173089.2:c.112C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173090.2:c.112C>T - 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
SCV001413083	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 10, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002085551	Natera, Inc.	no assertion criteria provided	Uncertain significance (Feb 13, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001413083

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 10, 2022)

germline

clinical testing

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

SCV002085551

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Feb 13, 2020)

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 Invitae, SCV001413083.2

#	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 phenylalanine, which is neutral and non-polar, at codon 703 of the CAPN3 protein (p.Leu703Phe). This variant is present in population databases (rs751443759, gnomAD 0.03%). 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: 965655). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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., SCV002085551.1

#	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: Jul 7, 2024

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