NM_000431.4(MVK):c.680C>G (p.Ser227Trp) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 7, 2022
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:: RCV002958840.2

Allele description

NM_000431.4(MVK):c.680C>G (p.Ser227Trp)

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.680C>G (p.Ser227Trp)

HGVS:

NC_000012.12:g.109590773C>G
NG_007702.1:g.22079C>G
NM_000431.4:c.680C>GMANE SELECT
NM_001114185.3:c.680C>G
NM_001301182.2:c.524C>G
NM_001414511.1:c.680C>G
NM_001414512.1:c.755C>G
NM_001414513.1:c.680C>G
NM_001414514.1:c.524C>G
NM_001414515.1:c.98C>G
NP_000422.1:p.Ser227Trp
NP_000422.1:p.Ser227Trp
NP_001107657.1:p.Ser227Trp
NP_001288111.1:p.Ser175Trp
NP_001401440.1:p.Ser227Trp
NP_001401441.1:p.Ser252Trp
NP_001401442.1:p.Ser227Trp
NP_001401443.1:p.Ser175Trp
NP_001401444.1:p.Ser33Trp
LRG_156t1:c.680C>G
LRG_156:g.22079C>G
LRG_156p1:p.Ser227Trp
NC_000012.11:g.110028578C>G
NM_000431.2:c.680C>G
NR_182758.1:n.892C>G
NR_182759.1:n.629C>G
NR_182762.1:n.473C>G

Protein change:

S175W

Molecular consequence:

NM_000431.4:c.680C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001114185.3:c.680C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301182.2:c.524C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001414511.1:c.680C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001414512.1:c.755C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001414513.1:c.680C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001414514.1:c.524C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001414515.1:c.98C>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003280683	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 7, 2022)	germline	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

SCV003280683

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 7, 2022)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003280683.2

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

Description

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. 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. This variant has not been reported in the literature in individuals affected with MVK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 227 of the MVK protein (p.Ser227Trp).

#	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: Feb 28, 2024

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