Submissions for variant NM_000243.3(MEFV):c.1508C>G (p.Ser503Cys)

gnomAD frequency: 0.00001  dbSNP: rs190705322

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000530643	SCV000629025	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 cysteine, which is neutral and slightly polar, at codon 503 of the MEFV protein (p.Ser503Cys). This variant is present in population databases (rs190705322, gnomAD 0.1%). This missense change has been observed in individual(s) with typical and atypical familial Mediterranean fever (PMID: 19531756, 21413889, 24797171, 30546872, 33747591). ClinVar contains an entry for this variant (Variation ID: 457996). 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.
Mendelics	RCV000530643	SCV001139850	uncertain significance	Familial Mediterranean fever	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001775848	SCV002013450	uncertain significance	not provided	2021-03-17	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified as a single heterozygous variant or phase unknown with other variants of uncertain significance in patients with MEFV-related disorders in published literature (Fujimoto et al., 2020; Wada et al., 2017; Kimura et al., 2018; Nakayama et al., 2017; Berdeli et al., 2011; Sugie et al., 2018); This variant is associated with the following publications: (PMID: 24252001, 31494649, 29151129, 31511485, 19531756, 24797171, 30546872, 21413889, 26247045, 27100444, 28956000, 32082075, 29526930, 29017770, 32475906, 33747591)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263738	SCV002543713	uncertain significance	Autoinflammatory syndrome	2021-12-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002490968	SCV002803917	uncertain significance	Familial Mediterranean fever; Familial Mediterranean fever, autosomal dominant; Acute febrile neutrophilic dermatosis	2021-11-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000530643	SCV003802107	uncertain significance	Familial Mediterranean fever	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126801	SCV003802108	likely benign	Familial Mediterranean fever, autosomal dominant	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126802	SCV003802109	likely benign	Acute febrile neutrophilic dermatosis	2023-02-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003126801	SCV004194404	likely pathogenic	Familial Mediterranean fever, autosomal dominant	2023-10-31	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000530643	SCV001338808	uncertain significance	Familial Mediterranean fever	2019-03-29	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000530643	SCV001452070	uncertain significance	Familial Mediterranean fever	2020-09-16	no assertion criteria provided	clinical testing