Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001307073 | SCV001496466 | pathogenic | Early myoclonic encephalopathy | 2021-11-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCND2 protein function. ClinVar contains an entry for this variant (Variation ID: 1009567). This missense change has been observed in individual(s) with clinical features of KCND2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 403 of the KCND2 protein (p.Pro403Leu). |
| Gene |
RCV001664818 | SCV001872869 | likely pathogenic | not provided | 2022-06-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV003284163 | SCV003954092 | likely pathogenic | Inborn genetic diseases | 2023-05-29 | criteria provided, single submitter | clinical testing | The c.1208C>T (p.P403L) alteration is located in exon 2 (coding exon 2) of the KCND2 gene. This alteration results from a C to T substitution at nucleotide position 1208, causing the proline (P) at amino acid position 403 to be replaced by a leucine (L). Another alteration at the same codon, c.1207C>G (p.P403A), has been reported de novo in an individual with features consistent with KCND2-related neurodevelopmental disorder (Zhang, 2021). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Based on internal structural analysis, P403L is deleterious as this variant disrupts a motif which is functionally important (Dinoi, 2022; Zhang, 2021; Barghaan, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |