ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.565G>T (p.Ala189Ser)

gnomAD frequency: 0.00001  dbSNP: rs1403009347
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001315807 SCV001506399 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2023-07-07 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Ala189 amino acid residue in MVK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30597534). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 1016754). This variant has not been reported in the literature in individuals affected with MVK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 189 of the MVK protein (p.Ala189Ser).
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002264264 SCV002542336 uncertain significance Autoinflammatory syndrome 2021-04-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001315807 SCV002793669 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2021-12-26 criteria provided, single submitter clinical testing

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