Submissions for variant NM_014845.5(FIG4):c.1940A>G (p.Tyr647Cys) (rs150301327)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Weber Lab,Hannover Medical School	RCV000416491	SCV000299298	likely pathogenic	Amyotrophic lateral sclerosis type 11	2016-09-13	criteria provided, single submitter	research
Invitae	RCV000688613	SCV000816233	uncertain significance	Charcot-Marie-Tooth disease type 4	2020-10-27	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine with cysteine at codon 647 of the FIG4 protein (p.Tyr647Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs150301327, ExAC 0.02%). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease (PMID: 25614874) and individuals affected with amyotropic lateral sclerosis (PMID: 19118816, 28051077). ClinVar contains an entry for this variant (Variation ID: 254671). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.
Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University	RCV001095518	SCV001251099	likely benign	not specified	2020-03-31	criteria provided, single submitter	research
Illumina Clinical Services Laboratory,Illumina	RCV001154064	SCV001315384	uncertain significance	Charcot-Marie-Tooth disease, type 4J	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV000416491	SCV001315385	uncertain significance	Amyotrophic lateral sclerosis type 11	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001172960	SCV001336035	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001508193	SCV001714179	uncertain significance	not provided	2021-01-19	criteria provided, single submitter	clinical testing