Submissions for variant NM_004960.4(FUS):c.188A>G (p.Asn63Ser)

gnomAD frequency: 0.00033  dbSNP: rs140883211

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000996260	SCV001150903	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858833	SCV002288257	uncertain significance	Amyotrophic lateral sclerosis type 6; Tremor, hereditary essential, 4	2024-12-04	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 63 of the FUS protein (p.Asn63Ser). This variant is present in population databases (rs140883211, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 19741216). ClinVar contains an entry for this variant (Variation ID: 808036). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics	RCV002409325	SCV002719406	likely benign	Inborn genetic diseases	2019-11-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Breakthrough Genomics, Breakthrough Genomics	RCV000996260	SCV005194332	uncertain significance	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003928643	SCV004737427	likely benign	FUS-related disorder	2022-06-27	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).