NM_003673.4(TCAP):c.110+5G>A AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 5, 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:: RCV001364211.5

Allele description [Variation Report for NM_003673.4(TCAP):c.110+5G>A]

NM_003673.4(TCAP):c.110+5G>A

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_003673.4(TCAP):c.110+5G>A

HGVS:

NC_000017.11:g.39665474G>A
NG_008892.1:g.5129G>A
NG_042278.1:g.2494G>A
NM_003673.4:c.110+5G>AMANE SELECT
LRG_210:g.5129G>A
NC_000017.10:g.37821727G>A

Links:

dbSNP: rs794729178

NCBI 1000 Genomes Browser:

rs794729178

Molecular consequence:

NM_003673.4:c.110+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Hypertrophic cardiomyopathy 25 (CMH25)
Synonyms:: 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
SCV001560346	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 5, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 32761539, 17576681, 9536098, 32005491, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001560346

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 5, 2023)

germline

clinical testing

PubMed (5)
[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

Distal myopathy due to TCAP variants in four unrelated Chinese patients.

Lv X, Gao F, Dai T, Zhao D, Jiang W, Geng H, Liu F, Lin P, Yan C.

Neurogenetics. 2021 Mar;22(1):1-10. doi: 10.1007/s10048-020-00623-4. Epub 2020 Aug 6.

PubMed [citation]

PMID:: 32761539

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001560346.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change falls in intron 1 of the TCAP gene. It does not directly change the encoded amino acid sequence of the TCAP protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 32005491, 32761539). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1055526). Studies have shown that this variant alters TCAP gene expression (PMID: 32005491). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 32005491). 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: Oct 8, 2024

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