NM_001001430.2(TNNT2):c.257A>C (p.Asp86Ala) AND Familial hypertrophic cardiomyopathy 2

Clinical significance:Likely pathogenic (Last evaluated: Nov 14, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000036571.2

Allele description [Variation Report for NM_001001430.2(TNNT2):c.257A>C (p.Asp86Ala)]

NM_001001430.2(TNNT2):c.257A>C (p.Asp86Ala)

Gene:
TNNT2:troponin T type 2 (cardiac) [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.1
Genomic location:
Preferred name:
NM_001001430.2(TNNT2):c.257A>C (p.Asp86Ala)
HGVS:
  • NC_000001.11:g.201365617T>G
  • NG_007556.1:g.17061A>C
  • NM_000364.3:c.287A>C
  • NM_001001430.2:c.257A>C
  • NP_000355.2:p.Asp96Ala
  • NP_001001430.1:p.Asp86Ala
  • NC_000001.10:g.201334745T>G
  • NM_001001430.1:c.257A>C
  • c.257A>C
  • p.D86A:GAC>GCC
Protein change:
D86A
Links:
dbSNP: 397516455
NCBI 1000 Genomes Browser:
rs397516455
Molecular consequence:
  • NM_001001430.2:c.257A>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Familial hypertrophic cardiomyopathy 2 (CMH2)
Synonyms:
TNNT2-Related Familial Hypertrophic Cardiomyopathy
Identifiers:
MedGen: C1861864; OMIM: 115195

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000060226Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
(LMM Criteria)
Likely pathogenic
(Nov 14, 2014)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided52not providednot providednot providedclinical testing

Citations

PubMed

Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy.

Van Driest SL, Ellsworth EG, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ.

Circulation. 2003 Jul 29;108(4):445-51. Epub 2003 Jul 14.

PubMed [citation]
PMID:
12860912

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,Partners HealthCare Personalized Medicine, SCV000060226.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (2)

Description

The p.Asp86Ala variant in TNNT2 has been previously reported in 1 adult with HCM (Van Driest 2003) and was identified by our laboratory in 2 Caucasian adults with HCM and segregated with disease in 1 affected relative (LMM unpublished data). Data from large population studies is insufficient to assess the frequency of this variant. Aspartic acid (Asp) at position 86 is highly conserved in mammals and across evolutionarily distant species and the change to alanine (Ala) was predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, although additional studies are required to fully establish its clinical significance, the p.Asp86Ala variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided5not provided2not provided

Last Updated: Jan 20, 2016