NM_000070.3(CAPN3):c.1706T>C (p.Phe569Ser) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 19, 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:: RCV003517180.2

Allele description [Variation Report for NM_000070.3(CAPN3):c.1706T>C (p.Phe569Ser)]

NM_000070.3(CAPN3):c.1706T>C (p.Phe569Ser)

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.1706T>C (p.Phe569Ser)

HGVS:

NC_000015.10:g.42402963T>C
NG_008660.1:g.59861T>C
NM_000070.3:c.1706T>CMANE SELECT
NM_024344.2:c.1706T>C
NM_173087.2:c.1562T>C
NM_173088.2:c.170T>C
NP_000061.1:p.Phe569Ser
NP_077320.1:p.Phe569Ser
NP_775110.1:p.Phe521Ser
NP_775111.1:p.Phe57Ser
LRG_849t1:c.1706T>C
LRG_849:g.59861T>C
LRG_849p1:p.Phe569Ser
NC_000015.9:g.42695161T>C

Protein change:

F521S

Links:

dbSNP: rs886044483

NCBI 1000 Genomes Browser:

rs886044483

Molecular consequence:

NM_000070.3:c.1706T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.1706T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.1562T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_173088.2:c.170T>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

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Homo sapiens ribonuclease P/MRP 14kDa subunit, mRNA (cDNA clone MGC:1868 IMAGE:3...
Homo sapiens ribonuclease P/MRP 14kDa subunit, mRNA (cDNA clone MGC:1868 IMAGE:3347003), complete cds
gi|45708499|gb|BC002441.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004296937	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 19, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16141003, 21204801, 32403337, 32896923, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004296937

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 19, 2023)

germline

clinical testing

PubMed (5)
[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

Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes.

Piluso G, Politano L, Aurino S, Fanin M, Ricci E, Ventriglia VM, Belsito A, Totaro A, Saccone V, Topaloglu H, Nascimbeni AC, Fulizio L, Broccolini A, Canki-Klain N, Comi LI, Nigro G, Angelini C, Nigro V.

J Med Genet. 2005 Sep;42(9):686-93.

PubMed [citation]

PMID:: 16141003
PMCID:: PMC1736133

Eosinophilic infiltration related to CAPN3 mutations: a pathophysiological component of primary calpainopathy?

Krahn M, Goicoechea M, Hanisch F, Groen E, Bartoli M, Pécheux C, Garcia-Bragado F, Leturcq F, Jeannet PY, Lobrinus JA, Jacquemont S, Strober J, Urtizberea JA, Saenz A, Bushby K, Lévy N, Lopez de Munain A.

Clin Genet. 2011 Oct;80(4):398-402. doi: 10.1111/j.1399-0004.2010.01620.x. No abstract available.

PubMed [citation]

PMID:: 21204801

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004296937.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 569 of the CAPN3 protein (p.Phe569Ser). 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. ClinVar contains an entry for this variant (Variation ID: 290547). This missense change has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 16141003, 21204801, 32403337, 32896923; Invitae). This variant is not present in population databases (gnomAD no frequency).

#	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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