Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000723946 | SCV000224482 | uncertain significance | not provided | 2018-09-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001082507 | SCV000288913 | likely benign | Brugada syndrome 8 | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000723946 | SCV000321764 | likely benign | not provided | 2021-05-28 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 29588962, 28341588, 30847666) |
Ambry Genetics | RCV000618430 | SCV000735071 | likely benign | Cardiovascular phenotype | 2018-07-22 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Center for Advanced Laboratory Medicine, |
RCV000852712 | SCV000995426 | likely benign | Primary dilated cardiomyopathy; Cardiomyopathy | 2019-06-11 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001117433 | SCV001275619 | uncertain significance | Sick sinus syndrome 2, autosomal dominant | 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. |
Center for Genomics, |
RCV003224176 | SCV003920028 | uncertain significance | Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 | 2021-03-30 | criteria provided, single submitter | clinical testing | HCN4 NM_005477.2 exon 1 p.Glu153Gly (c.458A>G): This variant has been reported in the literature in one individual with genearlized epilepsy and in one individual with unspecified cardiac arrhythmia (Becker 2017 PMID:29588962, Proost 2017 PMID:28341588). This variant did not segregate with disease in at least four affected family members with epilepsy (Becker 2017 PMID:29588962). This variant is present in 0.1% (31/14734) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/15-73660154-T-C). This variant is present in ClinVar (Variation ID:180370). This variant amino acid Glycine (Gly) is present in several bird and fish species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. However, an in vitro functional study using voltage clamp anaylsis does predict that this variant will impact the protein by causing a hyperpolarizing shift in activation and reduced current amplitudes (Becker 2017 PMID:29588962). However, this study may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Ce |
RCV000723946 | SCV004132801 | benign | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | HCN4: PP3, BS1, BS2 |
Blueprint Genetics | RCV000157245 | SCV000206972 | uncertain significance | Brugada syndrome | 2014-10-28 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000723946 | SCV001742089 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000723946 | SCV001920653 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000723946 | SCV001931500 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000723946 | SCV001958798 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000723946 | SCV001971864 | likely benign | not provided | no assertion criteria provided | clinical testing |