NM_003673.4(TCAP):c.110_110+1del AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 2021
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:: RCV001851683.3

Allele description [Variation Report for NM_003673.4(TCAP):c.110_110+1del]

NM_003673.4(TCAP):c.110_110+1del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_003673.4(TCAP):c.110_110+1del

HGVS:

NC_000017.11:g.39665469_39665470del
NG_008892.1:g.5124_5125del
NG_042278.1:g.2489_2490del
NM_003673.4:c.110_110+1delMANE SELECT
LRG_210t1:c.110_110+1del
LRG_210:g.5124_5125del
NC_000017.10:g.37821720_37821721del
NC_000017.10:g.37821722_37821723del
NM_003673.3:c.109_110del
NM_003673.3:c.110_110+1delGG

Note:

NCBI staff reviewed the sequence information reported in PubMed 10655062 Fig. 4 to determine the location of this allele on the current reference sequence.

Links:

OMIM: 604488.0002; dbSNP: rs786205076

NCBI 1000 Genomes Browser:

rs786205076

Molecular consequence:

NM_003673.4:c.110_110+1del - splice donor variant - [Sequence Ontology: SO:0001575]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002238753	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2021)	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

SCV002238753

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2021)

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, SCV002238753.3

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

Description

This sequence change creates a premature translational stop signal (p.Gly37Leufs*5) in the TCAP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 131 amino acid(s) of the TCAP protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy type 2G (PMID: 10655062). It has also been observed to segregate with disease in related individuals. This variant is also known as c.110_110+1del. ClinVar contains an entry for this variant (Variation ID: 5526). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. For these reasons, this variant has been classified as 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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