ClinVar Miner

Submissions for variant NM_004975.4(KCNB1):c.908G>A (p.Arg303Gln)

dbSNP: rs1057518621
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413312 SCV000492428 likely pathogenic not provided 2016-12-09 criteria provided, single submitter clinical testing The R303Q variant in the KCNB1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R303Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R303Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The R303Q variant is a strong candidate for a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000699040 SCV000827735 likely pathogenic Developmental and epileptic encephalopathy, 26 2020-11-21 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual with features consistent with a KCNB1-related condition (Invitae). ClinVar contains an entry for this variant (Variation ID: 373805). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 303 of the KCNB1 protein (p.Arg303Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine.

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