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NM_000431.4(MVK):c.60T>A (p.His20Gln) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 22, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003764776.1

Allele description [Variation Report for NM_000431.4(MVK):c.60T>A (p.His20Gln)]

NM_000431.4(MVK):c.60T>A (p.His20Gln)

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.60T>A (p.His20Gln)
HGVS:
  • NC_000012.12:g.109574882T>A
  • NG_007096.1:g.3616A>T
  • NG_007702.1:g.6188T>A
  • NM_000431.4:c.60T>AMANE SELECT
  • NM_001114185.3:c.60T>A
  • NM_001301182.2:c.60T>A
  • NP_000422.1:p.His20Gln
  • NP_001107657.1:p.His20Gln
  • NP_001288111.1:p.His20Gln
  • LRG_156:g.6188T>A
  • NC_000012.11:g.110012687T>A
  • NM_000431.1:c.60T>A
  • NM_000431.3:c.60T>A
  • Q03426:p.His20Gln
Protein change:
H20Q
Links:
UniProtKB: Q03426#VAR_029519; dbSNP: rs104895335
NCBI 1000 Genomes Browser:
rs104895335
Molecular consequence:
  • NM_000431.4:c.60T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114185.3:c.60T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301182.2:c.60T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mevalonic aciduria (MEVA)
Identifiers:
MONDO: MONDO:0012481; 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; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009849; MedGen: C0398691; Orphanet: 343; OMIM: 260920

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004570799Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 22, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever.

D'Osualdo A, Picco P, Caroli F, Gattorno M, Giacchino R, Fortini P, Corona F, Tommasini A, Salvi G, Specchia F, Obici L, Meini A, Ricci A, Seri M, Ravazzolo R, Martini A, Ceccherini I.

Eur J Hum Genet. 2005 Mar;13(3):314-20.

PubMed [citation]
PMID:
15536479

Phenotypic diversity, disease progression, and pathogenicity of MVK missense variants in mevalonic aciduria.

Brennenstuhl H, Nashawi M, Schröter J, Baronio F, Beedgen L, Gleich F, Jeltsch K, von Landenberg C, Martini S, Simon A, Thiel C, Tsiakas K, Opladen T, Kölker S, Hoffmann GF, Haas D; Unified Registry for Inherited Metabolic Disorders (U-IMD) Consortium and the European Registry for Hereditary Metabolic Disorders (MetabERN)..

J Inherit Metab Dis. 2021 Sep;44(5):1272-1287. doi: 10.1002/jimd.12412. Epub 2021 Jun 28.

PubMed [citation]
PMID:
34145613
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004570799.1

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

Description

This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 20 of the MVK protein (p.His20Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive mevalonate kinase deficiency (PMID: 15536479, 34145613). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 97602). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MVK protein function. This variant disrupts the p.His20 amino acid residue in MVK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11313769, 27213830, 28501347). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Jun 23, 2024