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NM_003673.4(TCAP):c.269C>T (p.Pro90Leu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 21, 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:
RCV000640703.8

Allele description [Variation Report for NM_003673.4(TCAP):c.269C>T (p.Pro90Leu)]

NM_003673.4(TCAP):c.269C>T (p.Pro90Leu)

Gene:
TCAP:titin-cap [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q12
Genomic location:
Preferred name:
NM_003673.4(TCAP):c.269C>T (p.Pro90Leu)
HGVS:
  • NC_000017.11:g.39665874C>T
  • NG_008892.1:g.5529C>T
  • NG_042278.1:g.2894C>T
  • NM_003673.4:c.269C>TMANE SELECT
  • NP_003664.1:p.Pro90Leu
  • NP_003664.1:p.Pro90Leu
  • LRG_210t1:c.269C>T
  • LRG_210:g.5529C>T
  • LRG_210p1:p.Pro90Leu
  • NC_000017.10:g.37822127C>T
  • NM_003673.3:c.269C>T
  • O15273:p.Pro90Leu
Protein change:
P90L
Links:
UniProtKB: O15273#VAR_026651; dbSNP: rs727504427
NCBI 1000 Genomes Browser:
rs727504427
Molecular consequence:
  • NM_003673.4:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000762300Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 21, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin.

Bos JM, Poley RN, Ny M, Tester DJ, Xu X, Vatta M, Towbin JA, Gersh BJ, Ommen SR, Ackerman MJ.

Mol Genet Metab. 2006 May;88(1):78-85. Epub 2005 Dec 13.

PubMed [citation]
PMID:
16352453
PMCID:
PMC2756511

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]
PMID:
27532257
PMCID:
PMC5116235
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000762300.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 177970). This missense change has been observed in individual(s) with either hypertrophic cardiomyopathy (HCM) and/or dilated cardiomyopathy (DCM) (PMID: 16352453, 27532257). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 90 of the TCAP protein (p.Pro90Leu).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 16, 2024