Submissions for variant NM_000238.4(KCNH2):c.77-5C>G

dbSNP: rs72549419

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001095172	SCV000467533	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000358645	SCV000555914	likely benign	Long QT syndrome	2025-01-30	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000712084	SCV000842501	likely benign	not provided	2018-01-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841275	SCV000903105	benign	Cardiac arrhythmia	2020-01-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000712084	SCV001860418	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411254	SCV002672184	likely benign	Cardiovascular phenotype	2018-04-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000712084	SCV004010742	benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	KCNH2: BP4, BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000712084	SCV004562372	likely benign	not provided	2023-03-22	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001700351	SCV001925901	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000712084	SCV001959461	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004549818	SCV004720243	likely benign	KCNH2-related disorder	2019-08-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).