Submissions for variant NM_000243.3(MEFV):c.1099C>G (p.Leu367Val)

gnomAD frequency: 0.00002  dbSNP: rs1057519328

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001805036	SCV002050834	uncertain significance	not specified	2021-12-09	criteria provided, single submitter	clinical testing	Variant summary: MEFV c.1099C>G (p.Leu367Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250532 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1099C>G has been reported in the literature in an individual affected with Behcets disease (Burillo-Sanz_2017). This report does not provide unequivocal conclusions about association of the variant with Familial Mediterranean Fever. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002480275	SCV002785331	uncertain significance	Familial Mediterranean fever; Familial Mediterranean fever, autosomal dominant; Acute febrile neutrophilic dermatosis	2021-09-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002521488	SCV003519166	uncertain significance	Familial Mediterranean fever	2022-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 367 of the MEFV protein (p.Leu367Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MEFV-related conditions (PMID: 28814775). ClinVar contains an entry for this variant (Variation ID: 375253). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine 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.
Genome-Nilou Lab	RCV002521488	SCV003802193	uncertain significance	Familial Mediterranean fever	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126718	SCV003802194	likely benign	Familial Mediterranean fever, autosomal dominant	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126719	SCV003802195	likely benign	Acute febrile neutrophilic dermatosis	2023-02-08	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003133255	SCV003810940	uncertain significance	not provided	2020-12-22	criteria provided, single submitter	clinical testing
Department of Immunology, Hospital Universitario Virgen del Rocio	RCV000416346	SCV000494058	pathogenic	Behcet disease	2017-01-25	no assertion criteria provided	case-control