ClinVar Miner

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

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Total submissions: 7
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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

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