ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.2315C>T (p.Pro772Leu)

gnomAD frequency: 0.00004  dbSNP: rs774206764
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000636332 SCV000757771 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2023-08-14 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 530457). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. This variant is present in population databases (rs774206764, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 772 of the KCNQ2 protein (p.Pro772Leu).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003403461 SCV004122286 uncertain significance not specified 2023-10-27 criteria provided, single submitter clinical testing Variant summary: KCNQ2 c.2315C>T (p.Pro772Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 192192 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2315C>T has been reported in the literature as a VUS in the heterozygous state in a setting of WES in an individual affected with epilepsy who also had other putatively pathogenic variants reported in epilepsy-related genes (Al Anazi_2022). This report does not provide unequivocal conclusions about association of the variant with KCNQ2-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 36539902). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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