NM_003476.5(CSRP3):c.436C>T (p.Arg146Cys) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 18, 2024
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:: RCV001071683.16

Allele description [Variation Report for NM_003476.5(CSRP3):c.436C>T (p.Arg146Cys)]

NM_003476.5(CSRP3):c.436C>T (p.Arg146Cys)

Gene:

CSRP3:cysteine and glycine rich protein 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_003476.5(CSRP3):c.436C>T (p.Arg146Cys)

HGVS:

NC_000011.10:g.19185024G>A
NG_011932.2:g.30550C>T
NM_001369404.1:c.267C>T
NM_003476.5:c.436C>TMANE SELECT
NP_001356333.1:p.Ser89=
NP_003467.1:p.Arg146Cys
LRG_440t1:c.436C>T
LRG_440:g.30550C>T
NC_000011.9:g.19206571G>A
NM_003476.3:c.436C>T
NM_003476.4:c.436C>T
NM_003476.5:c.436C>T

Protein change:

R146C

Links:

dbSNP: rs376198883

NCBI 1000 Genomes Browser:

rs376198883

Molecular consequence:

NM_003476.5:c.436C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369404.1:c.267C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Hypertrophic cardiomyopathy 12
Synonyms:: Familial hypertrophic cardiomyopathy 12
Identifiers:: MONDO: MONDO:0012804; MedGen: C2677491; OMIM: 612124

Name:: Dilated cardiomyopathy 1M (CMD1M)
Identifiers:: MONDO: MONDO:0011840; MedGen: C1843808; Orphanet: 154; OMIM: 607482

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001237000	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 18, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28790153, 28492532
SCV002789741	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 3, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001237000

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 18, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002789741

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 3, 2021)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	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

Multiple Gene Variants in Hypertrophic Cardiomyopathy in the Era of Next-Generation Sequencing.

Burns C, Bagnall RD, Lam L, Semsarian C, Ingles J.

Circ Cardiovasc Genet. 2017 Aug;10(4). doi:pii: e001666. 10.1161/CIRCGENETICS.116.001666.

PubMed [citation]

PMID:: 28790153

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001237000.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 146 of the CSRP3 protein (p.Arg146Cys). This variant is present in population databases (rs376198883, gnomAD 0.004%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 28790153). ClinVar contains an entry for this variant (Variation ID: 426380). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 Fulgent Genetics, Fulgent Genetics, SCV002789741.1

#	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

Last Updated: Mar 11, 2025

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