Submissions for variant NM_001037.5(SCN1B):c.23T>C (p.Val8Ala) (rs786205833)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000171048	SCV000223612	likely benign	not specified	2017-09-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000692873	SCV000820720	uncertain significance	Brugada syndrome 5	2018-03-13	criteria provided, single submitter	clinical testing	This sequence change replaces valine with alanine at codon 8 of the SCN1B protein (p.Val8Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SCN1B-related disease. ClinVar contains an entry for this variant (Variation ID: 190868). 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.