Submissions for variant NM_001376.5(DYNC1H1):c.10657C>G (p.Leu3553Val) (rs1595626695)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000821159	SCV000961906	uncertain significance	Charcot-Marie-Tooth disease, axonal, type 2O	2019-02-08	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with valine at codon 3553 of the DYNC1H1 protein (p.Leu3553Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DYNC1H1-related disease. 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. 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.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173998	SCV001337118	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing