ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.11231C>A (p.Thr3744Asn) (rs121912705)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171749 SCV000050753 likely benign Cardiac arrhythmia 2013-06-24 criteria provided, single submitter research
GeneDx RCV000223796 SCV000223265 likely benign not specified 2018-02-19 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723633 SCV000230577 uncertain significance not provided 2017-08-10 criteria provided, single submitter clinical testing
Invitae RCV000204635 SCV000260737 likely benign Long QT syndrome 2020-11-25 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000204635 SCV000263782 uncertain significance Long QT syndrome 2015-02-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618056 SCV000737813 likely benign Cardiovascular phenotype 2018-05-14 criteria provided, single submitter clinical testing Other data supporting benign classification;Subpopulation frequency in support of benign classification
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000723633 SCV000987420 likely benign not provided criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000723633 SCV001154264 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000019674 SCV001304614 uncertain significance Cardiac arrhythmia, ankyrin B-related 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000019674 SCV000039972 pathogenic Cardiac arrhythmia, ankyrin B-related 2004-06-15 no assertion criteria provided literature only
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058347 SCV000089867 not provided Arrhythmia no assertion provided literature only This variant has been reported as associated with Cardiac arrhythmia in the following publications (PMID:15178757). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000223796 SCV000280047 uncertain significance not specified 2015-10-12 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. We classify this variant as a variant of unknown significance. This variant has been previously reported in two unrelated individuals with borderline prolonged QT intervals (Mohler P et at., 2004; due to alternative nomenclature, they report it as Thr1626Asn). One of the reported individuals had a daughter, also heterozygous for the variant, who died suddenly at age 19 with no prior cardiac symptoms. All other carriers of the variant in the two families were asymptomatic. This is a conservative amino acid change, resulting in the replacement of a threonine (polar) with an asparagine (polar). Threonine at this location is conserved across most mammalian species for which data is available with the exception of the mouse and x-tropicalis. In silico analysis with PolyPhen-2 predicts the variant to be “possibly damaging” with a score of 0.951. In total, the variant has been seen in at least 12/6700 individuals from published controls and publicly available population datasets. This variant is listed in the NHLBI Exome Sequencing Project dataset, where it was found in 11 of 6503 genotyped individuals (2 of 2203 African Americans and 9 of 4300 European Americans), indicating that it may be a rare benign variant. Another variant affecting the same residue, T3744P, was also seen in 1 of 6503 genotyped individuals. This variant, T3744N, has been listed in dpSNP, but has not been documented in 1000 genomes. It was observed in 1 of 200 published control individuals of African American descent (Sherman J et al., 2005).

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