ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.1051C>T (p.Pro351Ser)

gnomAD frequency: 0.00005  dbSNP: rs773929129
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000701139 SCV000829923 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-08-08 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 351 of the MVK protein (p.Pro351Ser). This variant is present in population databases (rs773929129, gnomAD 0.0009%). 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: 578204). 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002446 SCV001160386 uncertain significance not specified 2019-03-27 criteria provided, single submitter clinical testing The MVK c.1051C>T; p.Pro351Ser variant (rs773929129), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is reported in the ClinVar database (Variation ID: 578204) and in the general population in 2 out of 248176 in the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at this position is weakly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. Due to limited information, the clinical significance of the variant is uncertain at this time.
Genetics and Molecular Pathology, SA Pathology RCV002466569 SCV002761365 uncertain significance Hyperimmunoglobulin D with periodic fever 2019-07-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000701139 SCV002775951 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2022-05-13 criteria provided, single submitter clinical testing

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