Submissions for variant NM_000431.4(MVK):c.298G>A (p.Asp100Asn)

gnomAD frequency: 0.00002  dbSNP: rs751713601

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001070922	SCV001236202	uncertain significance	Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever	2025-01-25	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 100 of the MVK protein (p.Asp100Asn). This variant is present in population databases (rs751713601, gnomAD 0.02%). 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: 863857). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The asparagine 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.
CeGaT Center for Human Genetics Tuebingen	RCV001090934	SCV001246717	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264178	SCV002542329	uncertain significance	Autoinflammatory syndrome	2016-12-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001070922	SCV005632683	likely benign	Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever	2024-03-08	criteria provided, single submitter	clinical testing