ClinVar Miner

Submissions for variant NM_000243.3(MEFV):c.1522C>G (p.Leu508Val)

gnomAD frequency: 0.00011  dbSNP: rs199937453
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001066615 SCV001231630 uncertain significance Familial Mediterranean fever 2022-06-23 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 508 of the MEFV protein (p.Leu508Val). This variant is present in population databases (rs199937453, gnomAD 0.05%). 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: 860331). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811638 SCV001473487 uncertain significance not provided 2019-09-30 criteria provided, single submitter clinical testing The MEFV c.1522C>G; p.Leu508Val variant (rs199937453), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the African population with an allele frequency of 0.048% (12/24970 alleles) in the Genome Aggregation Database. The leucine at codon 508 is highly conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: probably damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Leu508Val variant is uncertain at this time.
Genome-Nilou Lab RCV001066615 SCV003802100 uncertain significance Familial Mediterranean fever 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001274313 SCV003802102 likely benign Familial Mediterranean fever, autosomal dominant 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003127618 SCV003802103 likely benign Acute febrile neutrophilic dermatosis 2023-02-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV001274313 SCV001458301 uncertain significance Familial Mediterranean fever, autosomal dominant 2020-06-09 no assertion criteria provided clinical testing

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