NM_003673.4(TCAP):c.332dup (p.Gln112fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 20, 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:: RCV003789745.2

Allele description [Variation Report for NM_003673.4(TCAP):c.332dup (p.Gln112fs)]

NM_003673.4(TCAP):c.332dup (p.Gln112fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_003673.4(TCAP):c.332dup (p.Gln112fs)

HGVS:

NC_000017.11:g.39665937dup
NG_008892.1:g.5592dup
NG_042278.1:g.2957dup
NG_136447.1:g.270dup
NM_003673.4:c.332dupMANE SELECT
NP_003664.1:p.Gln112Profs
NP_003664.1:p.Gln112fs
LRG_210t1:c.332dup
LRG_210:g.5592dup
LRG_210p1:p.Gln112Profs
NC_000017.10:g.37822189_37822190insT
NC_000017.10:g.37822190dup
NM_003673.3:c.332dup

Protein change:

Q112fs

Molecular consequence:

NM_003673.4:c.332dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Lathyrus sativus, whole genome shotgun sequencing project
Lathyrus sativus, whole genome shotgun sequencing project
gi|2071209294|emb|CABITX000000000.1 TX010000000

Nucleotide

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
SCV004575861	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 20, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29970176, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004575861

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 20, 2022)

germline

clinical testing

PubMed (2)
[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

Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients.

Fichna JP, Macias A, Piechota M, Korostyński M, Potulska-Chromik A, Redowicz MJ, Zekanowski C.

Hum Genomics. 2018 Jul 3;12(1):34. doi: 10.1186/s40246-018-0167-1.

PubMed [citation]

PMID:: 29970176
PMCID:: PMC6029161

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004575861.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. This variant disrupts a region of the TCAP protein in which other variant(s) (p.Glu120Aspfs*15) have been observed in individuals with TCAP-related conditions (PMID: 29970176). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with TCAP-related conditions. This variant is present in population databases (rs770194856, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln112Profs*24) in the TCAP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 56 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: Oct 8, 2024

ClinVar

Relating variation to medicine