Submissions for variant NM_000243.3(MEFV):c.1016C>T (p.Ser339Phe)

gnomAD frequency: 0.00016  dbSNP: rs104895157

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000366739	SCV000329420	uncertain significance	not provided	2021-02-09	criteria provided, single submitter	clinical testing	Reported in a patient with periodic fever in published literature (Federici et al., 2012); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22580583, 28421071, 30476289, 26247045)
Invitae	RCV000030169	SCV000940571	uncertain significance	Familial Mediterranean fever	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 339 of the MEFV protein (p.Ser339Phe). This variant is present in population databases (rs104895157, gnomAD 0.06%). This missense change has been observed in individual(s) with familial Mediterranean fever (PMID: 21413889, 22580583, 22903357, 31989427). ClinVar contains an entry for this variant (Variation ID: 36497). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001001441	SCV001158679	uncertain significance	not specified	2019-02-15	criteria provided, single submitter	clinical testing	The MEFV c.1016C>T; p.Ser339Phe (rs104895157) is reported in the Infevers database in an individual without a described phenotype (see link below). The variant is reported in the ClinVar database (Variation ID: 36497) and in the general population with an overall allele frequency of 0.02% (50/279412 alleles) in the Genome Aggregation Database. The serine at this position is moderately conserved and computational analyses (SIFT: tolerated, PolyPhen-2: possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the variant is uncertain at this time. References: Link to Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=1
Illumina Laboratory Services, Illumina	RCV000030169	SCV001279958	uncertain significance	Familial Mediterranean fever	2017-06-14	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.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000366739	SCV001449584	uncertain significance	not provided	2024-01-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000030169	SCV001805999	uncertain significance	Familial Mediterranean fever	2021-07-14	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262577	SCV002543684	uncertain significance	Autoinflammatory syndrome	2018-07-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003466877	SCV004194409	uncertain significance	Familial Mediterranean fever, autosomal dominant	2024-04-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030169	SCV000052827	uncertain significance	Familial Mediterranean fever	2015-10-02	no assertion criteria provided	clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000030169	SCV000115765	not provided	Familial Mediterranean fever		no assertion provided	not provided
Natera, Inc.	RCV000030169	SCV001452082	uncertain significance	Familial Mediterranean fever	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000366739	SCV001927517	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000366739	SCV001953208	uncertain significance	not provided		no assertion criteria provided	clinical testing