ClinVar Miner

Submissions for variant NM_000243.3(MEFV):c.2048C>T (p.Ser683Leu)

gnomAD frequency: 0.00001  dbSNP: rs534682649
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001212071 SCV001383644 uncertain significance Familial Mediterranean fever 2021-12-04 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 683 of the MEFV protein (p.Ser683Leu). This variant is present in population databases (rs534682649, gnomAD 0.02%). 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: 942144). 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: "Tolerated"; 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.
Neuberg Centre For Genomic Medicine, NCGM RCV001212071 SCV005400762 uncertain significance Familial Mediterranean fever 2023-06-22 criteria provided, single submitter clinical testing The observed missense variant c.2048C>T(p.Ser683Leu) in MEFV gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2048C>T(p.Ser683Leu) variant is reported with 0.003% allele frequency in gnomAD Exomes. It has been submitted to ClinVar as Uncertain Significance. However, no details are available for independent assessment.The amino acid Ser at position 683 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen-probably damaging, SIFT-damaging and Mutation Taster-disease causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid p.Ser683Leu in MEFV is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Natera, Inc. RCV001212071 SCV002093889 uncertain significance Familial Mediterranean fever 2020-09-12 no assertion criteria provided clinical testing

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