Submissions for variant NM_000431.4(MVK):c.1156G>A (p.Asp386Asn)

gnomAD frequency: 0.00002  dbSNP: rs104895380

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001701591	SCV000513743	likely benign	not provided	2019-05-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27332769)
Invitae	RCV000887171	SCV001030716	benign	Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever	2024-01-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000083823	SCV001138813	likely benign	Hyperimmunoglobulin D with periodic fever	2019-05-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262659	SCV002542321	likely benign	Autoinflammatory syndrome	2021-04-05	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001701591	SCV004562261	uncertain significance	not provided	2023-09-20	criteria provided, single submitter	clinical testing	The MVK c.1156G>A; p.Asp386Asn variant (rs104895380) is reported in the literature in one individual where tumor necrosis factor receptor-associated periodic syndrome was suspected but the role of pathogenicity of this variant was unclear (Ueda 2016) and is reported in one individual with hyper-IgD syndrome (see Infevers database link). This variant is also reported in ClinVar (Variation ID: 97571). This variant is found in the South Asian population with an allele frequency of 0.9% (276/30616 alleles, including 7 homozygotes) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.319). While the high population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of this variant is uncertain at this time. References: Link to Infevers database: https://infevers.umai-montpellier.fr/web/ Ueda N et al. Clinical and Genetic Features of Patients With TNFRSF1A Variants in Japan: Findings of a Nationwide Survey. Arthritis Rheumatol. 2016 Nov;68(11):2760-2771. PMID: 27332769.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000083823	SCV000115925	not provided	Hyperimmunoglobulin D with periodic fever		no assertion provided	not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701591	SCV001928976	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001701591	SCV001964567	uncertain significance	not provided		no assertion criteria provided	clinical testing