ClinVar Miner

Submissions for variant NM_000243.3(MEFV):c.1337A>C (p.Glu446Ala)

gnomAD frequency: 0.00004  dbSNP: rs749651486
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000219419 SCV000279390 uncertain significance not provided 2020-09-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000632789 SCV000753977 uncertain significance Familial Mediterranean fever 2022-06-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 446 of the MEFV protein (p.Glu446Ala). This variant is present in population databases (rs749651486, gnomAD 0.008%). 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: 234502). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002262826 SCV002543701 uncertain significance Autoinflammatory syndrome 2018-07-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002478821 SCV002792336 uncertain significance Familial Mediterranean fever; Familial Mediterranean fever, autosomal dominant; Acute febrile neutrophilic dermatosis 2022-01-17 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000632789 SCV003802160 uncertain significance Familial Mediterranean fever 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003126637 SCV003802161 likely benign Familial Mediterranean fever, autosomal dominant 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003126638 SCV003802162 likely benign Acute febrile neutrophilic dermatosis 2023-02-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV000632789 SCV001452077 uncertain significance Familial Mediterranean fever 2020-09-16 no assertion criteria provided clinical testing

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