Submissions for variant NM_014845.6(FIG4):c.1999T>C (p.Tyr667His)

dbSNP: rs1777955968

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001047740	SCV001211720	uncertain significance	Charcot-Marie-Tooth disease type 4	2019-01-25	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine 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. This variant has not been reported in the literature in individuals with FIG4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 667 of the FIG4 protein (p.Tyr667His). The tyrosine residue is weakly conserved and there is a moderate physicochemical difference between tyrosine and histidine.
PreventionGenetics, part of Exact Sciences	RCV003898053	SCV004709140	uncertain significance	FIG4-related condition	2023-12-12	criteria provided, single submitter	clinical testing	The FIG4 c.1999T>C variant is predicted to result in the amino acid substitution p.Tyr667His. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.