NM_000363.5(TNNI3):c.304G>A (p.Ala102Thr) AND Hypertrophic cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Oct 10, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001238766.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.304G>A (p.Ala102Thr)]

NM_000363.5(TNNI3):c.304G>A (p.Ala102Thr)

Gene:
TNNI3:troponin I3, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.42
Genomic location:
Preferred name:
NM_000363.5(TNNI3):c.304G>A (p.Ala102Thr)
HGVS:
  • NC_000019.10:g.55154809C>T
  • NG_007866.2:g.7924G>A
  • NM_000363.5:c.304G>AMANE SELECT
  • NP_000354.4:p.Ala102Thr
  • LRG_432t1:c.304G>A
  • LRG_432:g.7924G>A
  • NC_000019.9:g.55666177C>T
  • NM_000363.4:c.304G>A
Protein change:
A102T
Links:
dbSNP: rs374618872
NCBI 1000 Genomes Browser:
rs374618872
Molecular consequence:
  • NM_000363.5:c.304G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; OMIM: PS192600; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001411595Invitaecriteria provided, single submitter
Uncertain significance
(Oct 10, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy.

Mademont-Soler I, Mates J, Yotti R, Espinosa MA, Pérez-Serra A, Fernandez-Avila AI, Coll M, Méndez I, Iglesias A, Del Olmo B, Riuró H, Cuenca S, Allegue C, Campuzano O, Picó F, Ferrer-Costa C, Álvarez P, Castillo S, Garcia-Pavia P, Gonzalez-Lopez E, Padron-Barthe L, Díaz de Bustamante A, et al.

PLoS One. 2017;12(8):e0181465. doi: 10.1371/journal.pone.0181465.

PubMed [citation]
PMID:
28771489
PMCID:
PMC5542623

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001411595.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine with threonine at codon 102 of the TNNI3 protein (p.Ala102Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs374618872, ExAC 0.01%). This variant has been observed in an individual with clinical features of hypertrophic cardiomyopathy (PMID: 28771489). ClinVar contains an entry for this variant (Variation ID: 165521). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0. The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Jul 7, 2021

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