Submissions for variant NM_000243.3(MEFV):c.1758T>C (p.Asn586=)

gnomAD frequency: 0.00003  dbSNP: rs202228332

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001116331	SCV001274394	uncertain significance	Familial Mediterranean fever	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001116331	SCV001391977	uncertain significance	Familial Mediterranean fever	2022-08-22	criteria provided, single submitter	clinical testing	This sequence change affects codon 586 of the MEFV mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MEFV protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs202228332, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MEFV-related conditions. ClinVar contains an entry for this variant (Variation ID: 884985). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Genome-Nilou Lab	RCV001116331	SCV003802053	benign	Familial Mediterranean fever	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003127633	SCV003802054	benign	Familial Mediterranean fever, autosomal dominant	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003127634	SCV003802055	benign	Acute febrile neutrophilic dermatosis	2023-02-08	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV001116331	SCV002029155	likely benign	Familial Mediterranean fever	2021-08-11	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001116331	SCV002087387	uncertain significance	Familial Mediterranean fever	2020-04-23	no assertion criteria provided	clinical testing