ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.97G>T (p.Val33Leu) (rs11466016)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768268 SCV000898828 uncertain significance Familial Mediterranean fever; Familial mediterranean fever, autosomal dominant 2017-11-21 criteria provided, single submitter clinical testing MEFV NM_000243.2 exon 1 p.Val33Leu (c.97G>T): This variant has not been reported in the literature but is present in 0.7% (191/24036) of African alleles including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs11466016). This variant is present in ClinVar (Variation ID:36516). This variant amino acid Leucine (Leu) is present in >40 species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV000589938 SCV000329418 uncertain significance not provided 2018-02-28 criteria provided, single submitter clinical testing To our knowledge, the V33L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant. The variant is observed in 191/24036 (0.79%) alleles from individuals of African background in large population cohorts, including one homozygote (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Integrated Genetics/Laboratory Corporation of America RCV000030189 SCV000052855 uncertain Familial Mediterranean fever 2011-08-18 criteria provided, single submitter curation Converted during submission to Uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000589938 SCV000696083 uncertain significance not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The MEFV c.97G>T (p.Val33Leu) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant . This variant was found in 99/121386 control chromosomes (2 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.009133 (95/10402). This frequency is about half of the estimated maximal expected allele frequency of a pathogenic MEFV variant (0.0216506). In addition, another clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

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