ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.3152C>T (p.Ser1051Leu)

gnomAD frequency: 0.00004  dbSNP: rs375749415
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Total submissions: 4
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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.
GeneDx 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.

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