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
Labcorp Genetics (formerly Invitae), Labcorp RCV000795579 SCV000935047 likely benign Developmental and epileptic encephalopathy, 14; Autosomal dominant nocturnal frontal lobe epilepsy 5 2024-12-30 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 uncertain significance Inborn genetic diseases 2024-10-28 criteria provided, single submitter clinical testing The c.3152C>T (p.S1051L) alteration is located in exon 27 (coding exon 27) of the KCNT1 gene. This alteration results from a C to T substitution at nucleotide position 3152, causing the serine (S) at amino acid position 1051 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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