NM_003476.5(CSRP3):c.535A>G (p.Thr179Ala) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 28, 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:: RCV000700094.7

Allele description [Variation Report for NM_003476.5(CSRP3):c.535A>G (p.Thr179Ala)]

NM_003476.5(CSRP3):c.535A>G (p.Thr179Ala)

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.535A>G (p.Thr179Ala)

HGVS:

NC_000011.10:g.19182720T>C
NG_011932.2:g.32854A>G
NM_001369404.1:c.366A>G
NM_003476.5:c.535A>GMANE SELECT
NP_001356333.1:p.Pro122=
NP_003467.1:p.Thr179Ala
LRG_440t1:c.535A>G
LRG_440:g.32854A>G
NC_000011.9:g.19204267T>C
NM_003476.3:c.535A>G
NM_003476.4:c.535A>G
c.535A>G

Protein change:

T179A

Links:

dbSNP: rs397516859

NCBI 1000 Genomes Browser:

rs397516859

Molecular consequence:

NM_003476.5:c.535A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369404.1:c.366A>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
SCV000828835	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24503780, 27532257, 28492532
SCV002787290	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 22, 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

SCV000828835

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 28, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002787290

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 22, 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

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000828835.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. 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. ClinVar contains an entry for this variant (Variation ID: 44701). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 24503780, 27532257). This variant is present in population databases (rs397516859, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 179 of the CSRP3 protein (p.Thr179Ala).

#	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, SCV002787290.1

#	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 5, 2024

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