ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.103580T>C (p.Ile34527Thr) (rs370618537)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000219152 SCV000271126 likely benign not specified 2015-06-24 criteria provided, single submitter clinical testing p.Ile31959Thr in exon 207 of TTN: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, >50 mammals have a threonine (Thr) at this position despite high nearby a mino acid conservation. It has also been identified in 4/66734 European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs370618537).
Ambry Genetics RCV000245827 SCV000318234 uncertain significance Cardiovascular phenotype 2013-02-18 criteria provided, single submitter clinical testing ​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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725877 SCV000701183 uncertain significance not provided 2017-01-03 criteria provided, single submitter clinical testing
Invitae RCV000643650 SCV000765337 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-12-11 criteria provided, single submitter clinical testing

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