Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000423575 | SCV000528566 | likely benign | not specified | 2017-03-02 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000423575 | SCV001442721 | benign | not specified | 2020-10-26 | criteria provided, single submitter | clinical testing | Variant summary: SCN1B c.207+13C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0001 in 143232 control chromosomes (gnomAD v3). The observed variant frequency is approximately 10 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN1B causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.207+13C>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. One co-occurrence with another pathogenic variant has been internally reported ( SCN5A c.5443_5446delTCTG , p.Ser1815ThrfsX18), providing supporting evidence for a benign role. One ClinVar submitter (evaluation after 2014) cites this variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Invitae | RCV002059698 | SCV002381419 | likely benign | Brugada syndrome 5 | 2024-01-11 | criteria provided, single submitter | clinical testing |