ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.663T>G (p.Ile221Met)

gnomAD frequency: 0.00018  dbSNP: rs757289914
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000792517 SCV000931820 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 221 of the MVK protein (p.Ile221Met). This variant is present in population databases (rs757289914, 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: 639662). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV000792517 SCV002794351 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-05-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV002535874 SCV003545068 uncertain significance Inborn genetic diseases 2021-07-02 criteria provided, single submitter clinical testing The c.663T>G (p.I221M) alteration is located in exon 7 (coding exon 6) of the MVK gene. This alteration results from a T to G substitution at nucleotide position 663, causing the isoleucine (I) at amino acid position 221 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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