Submissions for variant NM_001005360.2(DNM2):c.2231T>C (p.Val744Ala) (rs777609224)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000547445	SCV000640234	uncertain significance	Charcot-Marie-Tooth disease, dominant intermediate B	2018-04-09	criteria provided, single submitter	clinical testing	This sequence change replaces valine with alanine at codon 744 of the DNM2 protein (p.Val744Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs777609224, ExAC 0.005%). This variant has not been reported in the literature in individuals with DNM2-related disease. ClinVar contains an entry for this variant (Variation ID: 465284). 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.
GeneDx	RCV000834573	SCV000976344	likely benign	not provided	2018-05-25	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.