NM_003673.4(TCAP):c.34del (p.Glu12fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 9, 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:: RCV001949690.3

Allele description [Variation Report for NM_003673.4(TCAP):c.34del (p.Glu12fs)]

NM_003673.4(TCAP):c.34del (p.Glu12fs)

Gene:

TCAP:titin-cap [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_003673.4(TCAP):c.34del (p.Glu12fs)

HGVS:

NC_000017.11:g.39665393del
NG_008892.1:g.5048del
NG_042278.1:g.2413del
NM_003673.4:c.34delMANE SELECT
NP_003664.1:p.Glu12fs
LRG_210:g.5048del
NC_000017.10:g.37821645del
NC_000017.10:g.37821646del

Protein change:

E12fs

Links:

dbSNP: rs1555606959

NCBI 1000 Genomes Browser:

rs1555606959

Molecular consequence:

NM_003673.4:c.34del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hypertrophic cardiomyopathy 25 (CMH25)
Synonyms:: Dilated cardiomyopathy 1N; CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 25
Identifiers:: MONDO: MONDO:0011843; MedGen: C4225408; OMIM: 607487

Name:: Primary familial hypertrophic cardiomyopathy (HCM)
Synonyms:: Hereditary ventricular hypertrophy; Idiopathic hypertrophic subaortic stenosis
Identifiers:: MONDO: MONDO:0024573; MeSH: D024741; MedGen: C0949658; OMIM: PS192600

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
SCV002243460	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 9, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10655062, 23479141, 25298746, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002243460

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 9, 2022)

germline

clinical testing

PubMed (4)
[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

Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin.

Moreira ES, Wiltshire TJ, Faulkner G, Nilforoushan A, Vainzof M, Suzuki OT, Valle G, Reeves R, Zatz M, Passos-Bueno MR, Jenne DE.

Nat Genet. 2000 Feb;24(2):163-6.

PubMed [citation]

PMID:: 10655062

Muscle phenotypic variability in limb girdle muscular dystrophy 2 G.

Paim JF, Cotta A, Vargas AP, Navarro MM, Valicek J, Carvalho E, da-Cunha AL Jr, Plentz E, Braz SV, Takata RI, Almeida CF, Vainzof M.

J Mol Neurosci. 2013 Jun;50(2):339-44. doi: 10.1007/s12031-013-9987-6. Epub 2013 Mar 12.

PubMed [citation]

PMID:: 23479141

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002243460.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TCAP protein in which other variant(s) (p.Gln53*) have been determined to be pathogenic (PMID: 10655062, 23479141, 25298746). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1459213). This variant has not been reported in the literature in individuals affected with TCAP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu12Argfs*17) in the TCAP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 156 amino acid(s) of the TCAP protein.

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine