NM_001267550.2(TTN):c.103580T>C (p.Ile34527Thr) AND Cardiovascular phenotype

Clinical significance:Uncertain significance (Last evaluated: Feb 18, 2013)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000245827.1

Allele description [Variation Report for NM_001267550.2(TTN):c.103580T>C (p.Ile34527Thr)]

NM_001267550.2(TTN):c.103580T>C (p.Ile34527Thr)

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.103580T>C (p.Ile34527Thr)
HGVS:
  • NC_000002.12:g.178533035A>G
  • NG_011618.3:g.302768T>C
  • NG_051363.1:g.15209A>G
  • NM_001256850.1:c.98657T>C
  • NM_001267550.2:c.103580T>CMANE SELECT
  • NM_003319.4:c.76385T>C
  • NM_133378.4:c.95876T>C
  • NM_133432.3:c.76760T>C
  • NM_133437.4:c.76961T>C
  • NP_001243779.1:p.Ile32886Thr
  • NP_001254479.2:p.Ile34527Thr
  • NP_003310.4:p.Ile25462Thr
  • NP_596869.4:p.Ile31959Thr
  • NP_597676.3:p.Ile25587Thr
  • NP_597681.4:p.Ile25654Thr
  • LRG_391:g.302768T>C
  • NC_000002.11:g.179397762A>G
Protein change:
I25462T
Links:
dbSNP: rs370618537
NCBI 1000 Genomes Browser:
rs370618537
Molecular consequence:
  • NM_001256850.1:c.98657T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.103580T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.76385T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.95876T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.76760T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.76961T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000318234Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Feb 18, 2013)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000318234.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

​The p.I31959T variant (also known as c.95876T>C) is located in coding exon 306 of the TTN gene. This alteration results from a T to C substitution at nucleotide position 95876. The isoleucine at codon 31959 is replaced by threonine, an amino acid with similar properties. This variant was observed in conjunction with a pathogenic PKP2 mutation in a proband tested by our labortory who is affected with ADHD, sudden cardiac arrest and syncope. Based on data from the NHLBI Exome Sequencing Project (ESP), the C-allele has an overall frequency of approximately 0.01% (1/12,060), having been observed in 0% (0/3820) of African American alleles, and in 0.01% (1/8240) of European American alleles. Based on protein sequence alignment, this amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be benign by PolyPhen in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.I31959T remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Jul 7, 2021

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