NM_003673.4(TCAP):c.269C>T (p.Pro90Leu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 1, 2011
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:: RCV000154643.4

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]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000204318	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jul 1, 2011)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16352453, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000204318

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jul 1, 2011)

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	not provided	1	1	not provided	not provided	not provided	clinical 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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204318.5

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

Description

The Pro90Leu variant has been reported in one individual with HCM and was absent from 400 control chromosomes (200 White, 200 Black; Bos 2006). Of note, this i ndividual also carried a MYBPC3 variant of possible significance (Gln998Arg). O ur laboratory has detected the Pro90Leu variant in 1 Caucasian DCM proband (out of >336 Caucasian probands tested). Proline (Pro) at position 90 is conserved a cross evolutionary distant species, suggesting that a change would not be tolera ted. However it is not conserved in a single mammalian species (chimp has an al anine), making it difficult to interpret this data. Three computer tools (Polyp hen2, SIFT, MAPP) predict this change to be deleterious; however, their accuracy is unknown. In summary, additional data (functional/segregation/control studies ) is needed to determine the clinical significance of this variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Oct 13, 2024

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