Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693647 | SCV000821523 | likely pathogenic | Brugada syndrome 8 | 2022-07-05 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HCN4 protein function. Experimental studies have shown that this missense change affects HCN4 function (PMID: 25145517). ClinVar contains an entry for this variant (Variation ID: 374860). This missense change has been observed in individual(s) with HCN4-related conditions (PMID: 25145517, 27173043, 29447731). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 481 of the HCN4 protein (p.Tyr481His). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Institute of Human Genetics, |
RCV000415538 | SCV001428869 | pathogenic | Sick sinus syndrome 2, autosomal dominant | 2018-07-25 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000415538 | SCV000493946 | pathogenic | Sick sinus syndrome 2, autosomal dominant | 2014-08-26 | no assertion criteria provided | literature only | |
Diagnostic Laboratory, |
RCV001529223 | SCV001742311 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV001529223 | SCV001924626 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001529223 | SCV001927721 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001529223 | SCV001957700 | pathogenic | not provided | no assertion criteria provided | clinical testing |