NM_000431.4(MVK):c.1129G>A (p.Val377Ile) AND not specified

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 5, 2018
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:: RCV000999977.14

Allele description [Variation Report for NM_000431.4(MVK):c.1129G>A (p.Val377Ile)]

NM_000431.4(MVK):c.1129G>A (p.Val377Ile)

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.1129G>A (p.Val377Ile)

HGVS:

NC_000012.12:g.109596515G>A
NG_007702.1:g.27821G>A
NM_000431.4:c.1129G>AMANE SELECT
NM_001114185.3:c.1129G>A
NM_001301182.2:c.973G>A
NP_000422.1:p.Val377Ile
NP_001107657.1:p.Val377Ile
NP_001288111.1:p.Val325Ile
LRG_156t1:c.1129G>A
LRG_156:g.27821G>A
NC_000012.11:g.110034320G>A
NM_000431.2:c.1129G>A
NM_000431.3:c.1129G>A
NM_000431.4:c.1129G>A
NM_001114185.2:c.1129G>A
NM_001301182.1:c.973G>A
Q03426:p.Val377Ile

Protein change:

V325I; VAL377ILE

Links:

UniProtKB: Q03426#VAR_004027; OMIM: 251170.0002; dbSNP: rs28934897

NCBI 1000 Genomes Browser:

rs28934897

Molecular consequence:

NM_000431.4:c.1129G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114185.3:c.1129G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001301182.2:c.973G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000604326	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Jul 5, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000604326

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Jul 5, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000604326.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The MVK c.1129G>A;p.Val377Ile variant (rs28934897) is described in the medical literature in both the homozygous and compound heterozygous state in individuals with hyperimmunoglobulin D syndrome (HIDS) with reduced mevalonate kinase activity and has been implicated as the most common pathogenic HIDS variant (Houten 1999, Houten 2003). The variant is listed in the ClinVar database (Variation ID: 11929) and in the Genome Aggregation Database with an allele frequency of 0.16% (438/275368 alleles). Considering available information, this variant is classified as pathogenic. Pathogenic MVK variants are causative for autosomal recessive hyperimmunoglobulin D syndrome (HIDS, MIM: 260920) and mevalonic aciduria (MIM: 610377). References: Houten SM et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet. 1999 22(2):175-7. Houten SM et al. Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands. Eur J Hum Genet. 2003 11(2):196-200.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 15, 2024

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