NM_003476.5(CSRP3):c.472A>G (p.Asn158Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 3, 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:: RCV000653693.7

Allele description [Variation Report for NM_003476.5(CSRP3):c.472A>G (p.Asn158Asp)]

NM_003476.5(CSRP3):c.472A>G (p.Asn158Asp)

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.472A>G (p.Asn158Asp)

HGVS:

NC_000011.10:g.19184988T>C
NG_011932.2:g.30586A>G
NM_001369404.1:c.303A>G
NM_003476.5:c.472A>GMANE SELECT
NP_001356333.1:p.Gln101=
NP_003467.1:p.Asn158Asp
LRG_440:g.30586A>G
NC_000011.9:g.19206535T>C
NM_003476.4:c.472A>G

Protein change:

N158D

Links:

dbSNP: rs1373333255

NCBI 1000 Genomes Browser:

rs1373333255

Molecular consequence:

NM_003476.5:c.472A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369404.1:c.303A>G - 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
SCV000775576	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30847666, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000775576

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 3, 2023)

germline

clinical testing

PubMed (2)
[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

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]

PMID:: 30847666
PMCID:: PMC6533346

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

Details of each submission

From Invitae, SCV000775576.4

#	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 asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 158 of the CSRP3 protein (p.Asn158Asp). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with cardiomyopathy and/or hypertrophic cardiomyopathy (PMID: 30847666; Invitae). ClinVar contains an entry for this variant (Variation ID: 543038). 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 tolerated. 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

Last Updated: Jun 23, 2024

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