ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.898T>C (p.Ser300Pro) (rs1564356207)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000720293 SCV000851170 uncertain significance Seizures 2016-08-08 criteria provided, single submitter clinical testing The p.S300P variant (also known as c.898T>C), located in coding exon 11 of the KCNT1 gene, results from a T to C substitution at nucleotide position 898. The serine at codon 300 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved on species alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV001323228 SCV001514136 uncertain significance Early infantile epileptic encephalopathy 14; Epilepsy, nocturnal frontal lobe, 5 2020-06-04 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 300 of the KCNT1 protein (p.Ser300Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 589893). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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