NM_001267550.2(TTN):c.31505C>T (p.Ser10502Leu) AND not specified

Clinical significance:Likely benign (Last evaluated: Jan 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001174673.1

Allele description [Variation Report for NM_001267550.2(TTN):c.31505C>T (p.Ser10502Leu)]

NM_001267550.2(TTN):c.31505C>T (p.Ser10502Leu)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.31505C>T (p.Ser10502Leu)
HGVS:
  • NC_000002.12:g.178693930G>A
  • NG_011618.3:g.141873C>T
  • NM_001256850.1:c.30554C>T
  • NM_001267550.2:c.31505C>TMANE SELECT
  • NM_003319.4:c.13282+44152C>T
  • NM_133378.4:c.27773C>T
  • NM_133432.3:c.13657+44152C>T
  • NM_133437.4:c.13858+44152C>T
  • NP_001243779.1:p.Ser10185Leu
  • NP_001254479.2:p.Ser10502Leu
  • NP_596869.4:p.Ser9258Leu
  • LRG_391:g.141873C>T
  • NC_000002.11:g.179558657G>A
Protein change:
S10185L
Links:
dbSNP: rs768632287
NCBI 1000 Genomes Browser:
rs768632287
Molecular consequence:
  • NM_003319.4:c.13282+44152C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13657+44152C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13858+44152C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001256850.1:c.30554C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.31505C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.27773C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001337891Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Jan 6, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001337891.1

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

Description

Variant summary: TTN c.27773C>T (p.Ser9258Leu) results in a non-conservative amino acid change located in the I-band region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 248210 control chromosomes, predominantly at a frequency of 0.0011 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.76- fold the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.27773C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating an impact on protein function have been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory cited the variant as likely benign, and one laboratory cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Nov 27, 2021

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