Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000726913 | SCV000242640 | benign | not provided | 2020-12-07 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000726913 | SCV000704133 | uncertain significance | not provided | 2016-12-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001079061 | SCV000758013 | likely benign | Early infantile epileptic encephalopathy with suppression bursts | 2024-01-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002314754 | SCV000847504 | likely benign | Inborn genetic diseases | 2018-09-10 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469053 | SCV002766147 | likely benign | not specified | 2022-11-14 | criteria provided, single submitter | clinical testing | Variant summary: SCN1A c.5568G>A (p.Met1856Ile) results in a conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 250732 control chromosomes, predominantly at a frequency of 0.0014 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 78 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN1A causing SCN1A-Related Seizure Disorder phenotype (1.8e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.5568G>A in individuals affected with SCN1A-Related Seizure Disorder and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classifed the variant as VUS (n=1) and benign/likely benign (n=3). Based on the evidence outlined above, the variant was classified as likely benign. |