ClinVar Miner

Submissions for variant NM_000243.3(MEFV):c.1532C>T (p.Ala511Val)

gnomAD frequency: 0.00004  dbSNP: rs144270019
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000801307 SCV000941078 uncertain significance Familial Mediterranean fever 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 511 of the MEFV protein (p.Ala511Val). This variant is present in population databases (rs144270019, gnomAD 0.01%). This missense change has been observed in individual(s) with familial Mediterranean fever (PMID: 22281876). ClinVar contains an entry for this variant (Variation ID: 646921). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV000801307 SCV001139849 uncertain significance Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193207 SCV001361913 uncertain significance not specified 2019-08-15 criteria provided, single submitter clinical testing Variant summary: MEFV c.1532C>T (p.Ala511Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 251462 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (4e-05 vs 0.022), allowing no conclusion about variant significance. The variant, c.1532C>T, has been reported in the literature in individuals affected with Familial Mediterranean Fever (Akar_2010, Vergara_2012). These reports do 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002501072 SCV002776406 uncertain significance Familial Mediterranean fever; Familial Mediterranean fever, autosomal dominant; Acute febrile neutrophilic dermatosis 2022-05-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000801307 SCV003802094 likely benign Familial Mediterranean fever 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003126939 SCV003802095 benign Familial Mediterranean fever, autosomal dominant 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003126940 SCV003802096 benign Acute febrile neutrophilic dermatosis 2023-02-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV000801307 SCV001452068 uncertain significance Familial Mediterranean fever 2020-09-16 no assertion criteria provided clinical testing

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