ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.934_935delinsTT (p.Thr312Leu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000821814 SCV000962586 uncertain significance SeSAME syndrome 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with leucine at codon 312 of the KCNJ10 protein (p.Thr312Leu). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and leucine. This variant is reported as two separate single-nucleotide changes in population databases (c.934A>T, ExAC 0.006% and c.935C>T, ExAC 0.006%). However, in the read data for 5/5 individuals displayed in the ExAC browser, these two variants are in cis. This recapitulates the variant observed here (c.934_935delinsTT) and indicates that this variant is likely present in the population databases at 0.006%. This variant has not been reported in the literature in individuals with KCNJ10-related disease. 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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