NM_000070.3(CAPN3):c.1714C>T (p.Arg572Trp) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 25, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000725109.25

Allele description [Variation Report for NM_000070.3(CAPN3):c.1714C>T (p.Arg572Trp)]

NM_000070.3(CAPN3):c.1714C>T (p.Arg572Trp)

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.1714C>T (p.Arg572Trp)

HGVS:

NC_000015.10:g.42402971C>T
NG_008660.1:g.59869C>T
NM_000070.3:c.1714C>TMANE SELECT
NM_024344.2:c.1714C>T
NM_173087.2:c.1570C>T
NM_173088.2:c.178C>T
NP_000061.1:p.Arg572Trp
NP_077320.1:p.Arg572Trp
NP_775110.1:p.Arg524Trp
NP_775111.1:p.Arg60Trp
LRG_849t1:c.1714C>T
LRG_849:g.59869C>T
LRG_849p1:p.Arg572Trp
NC_000015.9:g.42695169C>T
NM_000070.2:c.1714C>T
P20807:p.Arg572Trp

Protein change:

R524W

Links:

UniProtKB: P20807#VAR_009590; dbSNP: rs863224959

NCBI 1000 Genomes Browser:

rs863224959

Molecular consequence:

NM_000070.3:c.1714C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.1714C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.1570C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173088.2:c.178C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000334064	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Oct 11, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15221789, 16141003, 16650086, 9150160 Citation Link,
SCV001247175	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2019)	germline	clinical testing	Citation Link,
SCV003921411	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 25, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000334064

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Oct 11, 2016)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV001247175

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jul 1, 2019)

germline

clinical testing

Citation Link,

SCV003921411

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 25, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	8	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular diagnosis in LGMD2A: mutation analysis or protein testing?

Fanin M, Fulizio L, Nascimbeni AC, Spinazzi M, Piluso G, Ventriglia VM, Ruzza G, Siciliano G, Trevisan CP, Politano L, Nigro V, Angelini C.

Hum Mutat. 2004 Jul;24(1):52-62.

PubMed [citation]

PMID:: 15221789

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

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000334064.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	8	not provided	not provided	clinical testing	PubMed (4)

#	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		8	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001247175.24

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

From GeneDx, SCV003921411.1

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

Description

Identified in additional individuals with LGMD for whom a second potentially pathogenic variant was not reported (Aguennouz et al., 2016; Tpf et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 31937337, 27558075, 32528171, 18563459, 9150160, 15221789, 27234031, 30919934, 30056071, 18854869, 17979987)

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

Last Updated: Aug 4, 2024

ClinVar

Relating variation to medicine