NM_000070.3(CAPN3):c.755T>C (p.Met252Thr) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 1, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV003140069.4

Allele description [Variation Report for NM_000070.3(CAPN3):c.755T>C (p.Met252Thr)]

NM_000070.3(CAPN3):c.755T>C (p.Met252Thr)

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.755T>C (p.Met252Thr)

HGVS:

NC_000015.10:g.42389050T>C
NG_008660.1:g.45948T>C
NM_000070.3:c.755T>CMANE SELECT
NM_024344.2:c.755T>C
NM_173087.2:c.755T>C
NP_000061.1:p.Met252Thr
NP_077320.1:p.Met252Thr
NP_775110.1:p.Met252Thr
LRG_849t1:c.755T>C
LRG_849:g.45948T>C
LRG_849p1:p.Met252Thr
NC_000015.9:g.42681248T>C
NM_000070.2:c.755T>C

Protein change:

M252T

Links:

dbSNP: rs1555420652

NCBI 1000 Genomes Browser:

rs1555420652

Molecular consequence:

NM_000070.3:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024344.2:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_173087.2:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003822488	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005078088	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Oct 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003822488

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 18, 2022)

germline

clinical testing

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

SCV005078088

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Oct 1, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Revvity Omics, Revvity, SCV003822488.2

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV005078088.1

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

Description

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; Identified with a second variant in an individual with limb girdle muscular dystrophy, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Fanin et al., 2009); Identified in an individual with limb girdle muscular dystrophy, but it is unknown whether this individual was tested for variants in other genes associated with muscular dystrophy (Piluso et al., 2005); This variant is associated with the following publications: (PMID: 18854869, 20635405, 16141003)

#	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: Sep 29, 2024

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