Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000795579 | SCV000935047 | likely benign | Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 | 2023-11-06 | criteria provided, single submitter | clinical testing | |
New York Genome Center | RCV001420547 | SCV001622852 | uncertain significance | Developmental and epileptic encephalopathy, 14 | 2020-06-19 | criteria provided, single submitter | clinical testing | The inherited c.3152C>T (p.Ser1051Leu) variant identified in the KCNT1 gene substitutes a moderately conserved Serine for Leucine at amino acid1051/1236 (coding exon 27/31). This variant is found with low frequency in gnomAD (v3.0)(5 heterozygotes, 0 homozygotes; allele frequency: 3.49e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Deleterious (Provean; score -2.58) and Damaging (SIFT; score:0.031) to the function of the canonical transcript. This variant is reported as a Variant of Uncertain Significance in ClinVar (VarID:642169) and to our current knowledge has not been reported in affected individuals in the literature. The p.Ser1051 residue is not within a mapped domain of KCNT1 (UniProtKB: Q5JUK3), and is located within the C-terminal cytoplasmic domain, however variants outside of mapped domains and within the C-terminal cytoplasmic domain have been identified in affected individuals in the literature [PMID:26122718]. Given the lack of compelling evidence for its pathogenicity, the c.3152C>T (p.Ser1051Leu) variant identified in the KCNT1 gene is reported here as a Variant of Uncertain Significance. |
Gene |
RCV001538360 | SCV001755999 | likely benign | not provided | 2020-12-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002325514 | SCV002610128 | likely benign | Inborn genetic diseases | 2020-06-08 | 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. |