NM_000363.5(TNNI3):c.596G>A (p.Ser199Asn) AND Hypertrophic cardiomyopathy

Clinical significance:Pathogenic (Last evaluated: Sep 2, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001239093.2

Allele description [Variation Report for NM_000363.5(TNNI3):c.596G>A (p.Ser199Asn)]

NM_000363.5(TNNI3):c.596G>A (p.Ser199Asn)

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.596G>A (p.Ser199Asn)
HGVS:
  • NC_000019.10:g.55151871C>T
  • NG_007866.2:g.10862G>A
  • NG_011829.2:g.2368G>A
  • NM_000363.5:c.596G>AMANE SELECT
  • NP_000354.4:p.Ser199Asn
  • LRG_432t1:c.596G>A
  • LRG_432:g.10862G>A
  • LRG_679:g.2368G>A
  • NC_000019.9:g.55663239C>T
  • NM_000363.4:c.596G>A
Protein change:
S199N
Links:
dbSNP: rs730881091
NCBI 1000 Genomes Browser:
rs730881091
Molecular consequence:
  • NM_000363.5:c.596G>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
SCV001411940Invitaecriteria provided, single submitter
Pathogenic
(Sep 2, 2020)
germlineclinical testing

PubMed (5)
[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

Malignant mutations in hypertrophic cardiomyopathy: fact or fancy?

Brito D, Madeira H.

Rev Port Cardiol. 2005 Sep;24(9):1137-46. Review. English, Portuguese.

PubMed [citation]
PMID:
16335287

Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives.

Andersen PS, Havndrup O, Hougs L, Sørensen KM, Jensen M, Larsen LA, Hedley P, Thomsen AR, Moolman-Smook J, Christiansen M, Bundgaard H.

Hum Mutat. 2009 Mar;30(3):363-70. doi: 10.1002/humu.20862.

PubMed [citation]
PMID:
19035361
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001411940.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces serine with asparagine at codon 199 of the TNNI3 protein (p.Ser199Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 15607392, 16335287, 19035361, 27532257). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 181603). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Ser199 amino acid residue in TNNI3. Other variant(s) that disrupt this residue have been observed in individuals with TNNI3-related conditions (PMID: 15607392), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

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