NM_003476.5(CSRP3):c.365G>A (p.Arg122Gln) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 12, 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:: RCV000653699.4

Allele description [Variation Report for NM_003476.5(CSRP3):c.365G>A (p.Arg122Gln)]

NM_003476.5(CSRP3):c.365G>A (p.Arg122Gln)

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.365G>A (p.Arg122Gln)

HGVS:

NC_000011.10:g.19186265C>T
NG_011932.2:g.29309G>A
NM_001369404.1:c.196G>A
NM_003476.5:c.365G>AMANE SELECT
NP_001356333.1:p.Asp66Asn
NP_003467.1:p.Arg122Gln
LRG_440t1:c.365G>A
LRG_440:g.29309G>A
NC_000011.9:g.19207812C>T
NM_003476.3:c.365G>A
NM_003476.4:c.365G>A

Protein change:

D66N

Links:

dbSNP: rs193922667

NCBI 1000 Genomes Browser:

rs193922667

Molecular consequence:

NM_001369404.1:c.196G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003476.5:c.365G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000775582	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 12, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33012304, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000775582

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 12, 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

Genetic study of pediatric hypertrophic cardiomyopathy in Egypt.

Darwish RK, Haghighi A, Seliem ZS, El-Saiedi SA, Radwan NH, El-Gayar DF, Elfeel NS, Abouelhoda M, Mehaney DA.

Cardiol Young. 2020 Dec;30(12):1910-1916. doi: 10.1017/S1047951120003157. Epub 2020 Oct 5.

PubMed [citation]

PMID:: 33012304

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, SCV000775582.4

#	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 122 of the CSRP3 protein (p.Arg122Gln). This variant is present in population databases (rs193922667, gnomAD 0.004%). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 33012304; Invitae). ClinVar contains an entry for this variant (Variation ID: 35966). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: May 1, 2024

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