NM_003476.5(CSRP3):c.377C>A (p.Ser126Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 12, 2022
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:: RCV003775729.1

Allele description [Variation Report for NM_003476.5(CSRP3):c.377C>A (p.Ser126Ter)]

NM_003476.5(CSRP3):c.377C>A (p.Ser126Ter)

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.377C>A (p.Ser126Ter)

HGVS:

NC_000011.10:g.19186253G>T
NG_011932.2:g.29321C>A
NM_001127656.1:c.377C>A
NM_001369404.1:c.208C>A
NM_003476.5:c.377C>AMANE SELECT
NP_001121128.1:p.Ser126Ter
NP_001356333.1:p.Gln70Lys
NP_003467.1:p.Ser126Ter
NP_003467.1:p.Ser126Ter
LRG_440t1:c.377C>A
LRG_440:g.29321C>A
LRG_440p1:p.Ser126Ter
NC_000011.9:g.19207800G>T
NM_003476.3:c.377C>A

Protein change:

Q70K

Molecular consequence:

NM_001369404.1:c.208C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127656.1:c.377C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003476.5:c.377C>A - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004581013	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 12, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12642359, 14567970, 16352453, 20087448, 34558151, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004581013

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 12, 2022)

germline

clinical testing

PubMed (6)
[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

Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy.

Geier C, Perrot A, Ozcelik C, Binner P, Counsell D, Hoffmann K, Pilz B, Martiniak Y, Gehmlich K, van der Ven PF, Fürst DO, Vornwald A, von Hodenberg E, Nürnberg P, Scheffold T, Dietz R, Osterziel KJ.

Circulation. 2003 Mar 18;107(10):1390-5.

PubMed [citation]

PMID:: 12642359

Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis.

Mohapatra B, Jimenez S, Lin JH, Bowles KR, Coveler KJ, Marx JG, Chrisco MA, Murphy RT, Lurie PR, Schwartz RJ, Elliott PM, Vatta M, McKenna W, Towbin JA, Bowles NE.

Mol Genet Metab. 2003 Sep-Oct;80(1-2):207-15.

PubMed [citation]

PMID:: 14567970

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004581013.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with CSRP3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser126*) in the CSRP3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSRP3 are known to be pathogenic (PMID: 12642359, 14567970, 16352453, 20087448, 34558151).

#	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

ClinVar

Relating variation to medicine