NM_000431.4(MVK):c.644G>A (p.Arg215Gln) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jun 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001383593.1

Allele description [Variation Report for NM_000431.4(MVK):c.644G>A (p.Arg215Gln)]

NM_000431.4(MVK):c.644G>A (p.Arg215Gln)

Gene:
MVK:mevalonate kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.11
Genomic location:
Preferred name:
NM_000431.4(MVK):c.644G>A (p.Arg215Gln)
HGVS:
  • NC_000012.12:g.109586766G>A
  • NG_007702.1:g.18072G>A
  • NM_000431.4:c.644G>AMANE SELECT
  • NM_001114185.3:c.644G>A
  • NM_001301182.2:c.488G>A
  • NP_000422.1:p.Arg215Gln
  • NP_001107657.1:p.Arg215Gln
  • NP_001288111.1:p.Arg163Gln
  • LRG_156:g.18072G>A
  • NC_000012.11:g.110024571G>A
  • NM_000431.1:c.644G>A
  • Q03426:p.Arg215Gln
Protein change:
R163Q
Links:
UniProtKB: Q03426#VAR_010963; dbSNP: rs104895303
NCBI 1000 Genomes Browser:
rs104895303
Molecular consequence:
  • NM_000431.4:c.644G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114185.3:c.644G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301182.2:c.488G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mevalonic aciduria (MEVA)
Synonyms:
Mevalonate kinase deficiency
Identifiers:
MedGen: C1959626; Orphanet: 29; OMIM: 610377
Name:
Porokeratosis 3, disseminated superficial actinic type (DSAP1)
Synonyms:
Porokeratosis, disseminated superficial actinic 1; POROKERATOSIS 3, MULTIPLE TYPES; POROKERATOSIS 3, MIBELLI TYPE
Identifiers:
MONDO: MONDO:0008293; MedGen: C1867981; OMIM: 175900
Name:
Hyperimmunoglobulin D with periodic fever (HIDS)
Synonyms:
Hyperimmunoglobulinemia D and periodic fever syndrome; Periodic fever Dutch type; Hyperimmunoglobulinemia D
Identifiers:
MONDO: MONDO:0009849; MedGen: C0398691; Orphanet: 343; OMIM: 260920

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001582786Invitaecriteria provided, single submitter
Pathogenic
(Jun 1, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome.

Cuisset L, Drenth JP, Simon A, Vincent MF, van der Velde Visser S, van der Meer JW, Grateau G, Delpech M; International Hyper-IgD Study Group..

Eur J Hum Genet. 2001 Apr;9(4):260-6.

PubMed [citation]
PMID:
11313769

Diagnostic Value of Urinary Mevalonic Acid Excretion in Patients with a Clinical Suspicion of Mevalonate Kinase Deficiency (MKD).

Jeyaratnam J, Ter Haar NM, de Sain-van der Velden MG, Waterham HR, van Gijn ME, Frenkel J.

JIMD Rep. 2016;27:33-8. doi: 10.1007/8904_2015_489. Epub 2015 Sep 27.

PubMed [citation]
PMID:
26409462
PMCID:
PMC4867845
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001582786.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces arginine with glutamine at codon 215 of the MVK protein (p.Arg215Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs104895303, ExAC 0.006%). This variant has been observed in individual(s) with mevalonate kinase deficiency (PMID: 11313769, 26409462, 27213830, 15536479). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 97608). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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