NM_001267550.2(TTN):c.95068G>A (p.Val31690Met) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Oct 27, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000152179.2

Allele description [Variation Report for NM_001267550.2(TTN):c.95068G>A (p.Val31690Met)]

NM_001267550.2(TTN):c.95068G>A (p.Val31690Met)

Genes:
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.95068G>A (p.Val31690Met)
HGVS:
  • NC_000002.12:g.178546263C>T
  • NG_011618.3:g.289540G>A
  • NG_051363.1:g.28437C>T
  • NM_001256850.1:c.90145G>A
  • NM_001267550.2:c.95068G>AMANE SELECT
  • NM_003319.4:c.67873G>A
  • NM_133378.4:c.87364G>A
  • NM_133432.3:c.68248G>A
  • NM_133437.4:c.68449G>A
  • NP_001243779.1:p.Val30049Met
  • NP_001254479.2:p.Val31690Met
  • NP_003310.4:p.Val22625Met
  • NP_596869.4:p.Val29122Met
  • NP_597676.3:p.Val22750Met
  • NP_597681.4:p.Val22817Met
  • LRG_391:g.289540G>A
  • NC_000002.11:g.179410990C>T
Protein change:
V22625M
Links:
dbSNP: rs727503543
NCBI 1000 Genomes Browser:
rs727503543
Molecular consequence:
  • NM_001256850.1:c.90145G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.95068G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.67873G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.87364G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.68248G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.68449G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000200915Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Feb 6, 2014)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001442846Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Oct 27, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided21not providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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, SCV000200915.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

The Val29122Met variant in TTN has not been reported in individuals with cardiom yopathy or in large population studies. Computational analyses (biochemical amin o acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information i s needed to fully assess the clinical significance of the Val29122Met variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided1not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001442846.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: TTN c.87364G>A (p.Val29122Met) results in a conservative amino acid change located in the A-band region of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 248580 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.87364G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Nov 27, 2021

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