ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.874C>T (p.Leu292Phe)

gnomAD frequency: 0.00004  dbSNP: rs145586352
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788518 SCV000927665 uncertain significance not provided 2018-04-30 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000788518 SCV001148819 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001037197 SCV001200598 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-08-12 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 292 of the MVK protein (p.Leu292Phe). This variant is present in population databases (rs145586352, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MVK-related conditions. ClinVar contains an entry for this variant (Variation ID: 636630). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MVK protein function with a negative predictive value of 80%. 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.
GeneDx RCV000788518 SCV001824785 uncertain significance not provided 2020-08-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002535777 SCV003754888 uncertain significance Inborn genetic diseases 2022-12-01 criteria provided, single submitter clinical testing The c.874C>T (p.L292F) alteration is located in exon 9 (coding exon 8) of the MVK gene. This alteration results from a C to T substitution at nucleotide position 874, causing the leucine (L) at amino acid position 292 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV000788518 SCV005408387 uncertain significance not provided 2023-12-29 criteria provided, single submitter clinical testing BP4, PM2_moderate

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