NM_000070.3(CAPN3):c.245C>T (p.Pro82Leu) AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 14, 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:: RCV000311426.10

Allele description [Variation Report for NM_000070.3(CAPN3):c.245C>T (p.Pro82Leu)]

NM_000070.3(CAPN3):c.245C>T (p.Pro82Leu)

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.245C>T (p.Pro82Leu)

HGVS:

NC_000015.10:g.42360050C>T
NG_008660.1:g.16948C>T
NM_000070.3:c.245C>TMANE SELECT
NM_024344.2:c.245C>T
NM_173087.2:c.245C>T
NP_000061.1:p.Pro82Leu
NP_077320.1:p.Pro82Leu
NP_775110.1:p.Pro82Leu
LRG_849t1:c.245C>T
LRG_849:g.16948C>T
LRG_849p1:p.Pro82Leu
NC_000015.9:g.42652248C>T
NM_000070.2:c.245C>T

Protein change:

P82L

Links:

dbSNP: rs886042478

NCBI 1000 Genomes Browser:

rs886042478

Molecular consequence:

NM_000070.3:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.245C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.245C>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

Recent activity

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Nucleotide
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gi|62752469|gb|AY790832.1|

Nucleotide
Brissopsis atlantica voucher 1151579 16S ribosomal RNA gene, partial sequence; m...
Brissopsis atlantica voucher 1151579 16S ribosomal RNA gene, partial sequence; mitochondrial
gi|2206982084|gnl|uoguelph|MOCIN202 6S|gb|MN868941.1|

Nucleotide
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gi|1489968300|gnl|uoguelph|FTMCA209 OI-5P|gb|MG421730.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000788754	Counsyl	no assertion criteria provided	Likely pathogenic (Dec 15, 2016)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000830891	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 14, 2023)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 12461690, 12890817, 15221789, 15351423, 16100770, 16141003, 16372320, 17157502, 20635405, 25135358, 26886200, 27447704, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000788754

Counsyl

no assertion criteria provided

Likely pathogenic
(Dec 15, 2016)

unknown

clinical testing

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

SCV000830891

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 14, 2023)

germline

clinical testing

PubMed (13)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical variability in calpainopathy: what makes the difference?

de Paula F, Vainzof M, Passos-Bueno MR, de Cássia M Pavanello R, Matioli SR, V B Anderson L, Nigro V, Zatz M.

Eur J Hum Genet. 2002 Dec;10(12):825-32.

PubMed [citation]

PMID:: 12461690

The effect of calpain 3 deficiency on the pattern of muscle degeneration in the earliest stages of LGMD2A.

Vainzof M, de Paula F, Tsanaclis AM, Zatz M.

J Clin Pathol. 2003 Aug;56(8):624-6.

PubMed [citation]

PMID:: 12890817
PMCID:: PMC1770017

See all PubMed Citations (13)

Details of each submission

From Counsyl, SCV000788754.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000830891.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 82 of the CAPN3 protein (p.Pro82Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 12461690, 12890817, 15221789, 15351423, 16100770, 16141003, 16372320, 17157502, 20635405, 25135358, 26886200, 27447704). ClinVar contains an entry for this variant (Variation ID: 282783). 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 not expected to disrupt CAPN3 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 20, 2024

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