NM_000431.4(MVK):c.1139A>G (p.His380Arg) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jul 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000690628.4

Allele description [Variation Report for NM_000431.4(MVK):c.1139A>G (p.His380Arg)]

NM_000431.4(MVK):c.1139A>G (p.His380Arg)

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.1139A>G (p.His380Arg)
HGVS:
  • NC_000012.12:g.109596525A>G
  • NG_007702.1:g.27831A>G
  • NM_000431.4:c.1139A>GMANE SELECT
  • NM_001114185.3:c.1139A>G
  • NM_001301182.2:c.983A>G
  • NP_000422.1:p.His380Arg
  • NP_001107657.1:p.His380Arg
  • NP_001288111.1:p.His328Arg
  • LRG_156:g.27831A>G
  • NC_000012.11:g.110034330A>G
  • NM_000431.1:c.1139A>G
  • NM_000431.3:c.1139A>G
Protein change:
H328R
Links:
dbSNP: rs104895324
NCBI 1000 Genomes Browser:
rs104895324
Molecular consequence:
  • NM_000431.4:c.1139A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114185.3:c.1139A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301182.2:c.983A>G - 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
SCV000818325Invitaecriteria provided, single submitter
Pathogenic
(Jul 23, 2020)
germlineclinical testing

PubMed (6)
[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

Henoch-Schönlein purpura in a child with hyperimmunoglobulinemia D and periodic fever syndrome.

Wickiser JE, Saulsbury FT.

Pediatr Dermatol. 2005 Mar-Apr;22(2):138-41.

PubMed [citation]
PMID:
15804303

Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome.

van der Hilst JCH, Bodar EJ, Barron KS, Frenkel J, Drenth JPH, van der Meer JWM, Simon A; International HIDS Study Group..

Medicine (Baltimore). 2008 Nov;87(6):301-310. doi: 10.1097/MD.0b013e318190cfb7.

PubMed [citation]
PMID:
19011501
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000818325.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces histidine with arginine at codon 380 of the MVK protein (p.His380Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs104895324, ExAC 0.008%). This variant has been reported in combination with another MVK variant in several individuals affected with hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) (PMID: 15804303, 19011501, 21399979, 24561416, 29047407), has been observed on the opposite chromosome (in trans) from a likely pathogenic variant in an affected individual (Invitae). ClinVar contains an entry for this variant (Variation ID: 97569). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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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