Submissions for variant NM_001365951.3(KIF1B):c.2846C>T (p.Thr949Met)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001048551	SCV001212564	uncertain significance	Charcot-Marie-Tooth disease, type 2	2019-12-05	criteria provided, single submitter	clinical testing	This sequence change replaces threonine with methionine at codon 903 of the KIF1B protein (p.Thr903Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs141942131, ExAC 0.01%). This variant has not been reported in the literature in individuals with KIF1B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0. The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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	RCV001173602	SCV001336702	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV001197631	SCV001368410	uncertain significance	Pheochromocytoma	2019-02-28	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: No criteria apply.