ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.2331C>T (p.Thr777=) (rs41307292)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001095234 SCV000467514 uncertain significance Long QT syndrome 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000419773 SCV000513227 likely benign not specified 2016-04-28 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000589926 SCV000696023 benign not provided 2016-10-31 criteria provided, single submitter clinical testing Variant summary: The c.2331T>C (p.Thr777=) in KCNH2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control population dataset of ExAC at a frequency of 0.0001 (13/120792 chrs tested), predominantly in individuals of East Asian descent (0.001; 9/8618 chrs tested). These frequencies exceed the estimated maximal expected allele frequency of a pathogenic variant in KCNH2 gene (0.0001). The variant has not, to our knowledge, been reported in affected individuals via publications but was reported as a polymorphism in healthy Chinese controls (Koo, 2006). A clinical diagnostic laboratory cites the variant as a "VOUS." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000589926 SCV000701670 uncertain significance not provided 2016-10-19 criteria provided, single submitter clinical testing
Invitae RCV000262824 SCV001013556 benign Long QT syndrome 2019-12-31 criteria provided, single submitter clinical testing
Color RCV001183983 SCV001349845 likely benign Arrhythmia 2018-11-18 criteria provided, single submitter clinical testing

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