NM_000431.4(MVK):c.511G>A (p.Gly171Arg) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 27, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001065483.4

Allele description [Variation Report for NM_000431.4(MVK):c.511G>A (p.Gly171Arg)]

NM_000431.4(MVK):c.511G>A (p.Gly171Arg)

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.511G>A (p.Gly171Arg)

HGVS:

NC_000012.12:g.109581534G>A
NG_007702.1:g.12840G>A
NM_000431.4:c.511G>AMANE SELECT
NM_001114185.3:c.511G>A
NM_001301182.2:c.371+1588G>A
NP_000422.1:p.Gly171Arg
NP_001107657.1:p.Gly171Arg
LRG_156:g.12840G>A
NC_000012.11:g.110019339G>A
NM_000431.1:c.511G>A
NM_000431.3:c.511G>A
Q03426:p.Gly171Arg

Protein change:

G171R

Links:

UniProtKB: Q03426#VAR_029521; dbSNP: rs104895337

NCBI 1000 Genomes Browser:

rs104895337

Molecular consequence:

NM_001301182.2:c.371+1588G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000431.4:c.511G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114185.3:c.511G>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001230442	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 27, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15536479, 21478439, 28492532
SCV002781892	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 27, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001230442

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 27, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002781892

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 27, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade.

Stojanov S, Lapidus S, Chitkara P, Feder H, Salazar JC, Fleisher TA, Brown MR, Edwards KM, Ward MM, Colbert RA, Sun HW, Wood GM, Barham BK, Jones A, Aksentijevich I, Goldbach-Mansky R, Athreya B, Barron KS, Kastner DL.

Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7148-53. doi: 10.1073/pnas.1103681108. Epub 2011 Apr 8.

PubMed [citation]

PMID:: 21478439
PMCID:: PMC3084055

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001230442.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine with arginine at codon 171 of the MVK protein (p.Gly171Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs104895337, ExAC 0.006%). This missense change has been observed in individuals with hyper-IgD and periodic fever syndrome (PMID: 15536479, 21478439). ClinVar contains an entry for this variant (Variation ID: 97595). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002781892.1

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

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

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine