NM_000431.4(MVK):c.346T>C (p.Tyr116His) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 25, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000220019.3

Allele description [Variation Report for NM_000431.4(MVK):c.346T>C (p.Tyr116His)]

NM_000431.4(MVK):c.346T>C (p.Tyr116His)

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.346T>C (p.Tyr116His)
HGVS:
  • NC_000012.12:g.109579921T>C
  • NG_007702.1:g.11227T>C
  • NM_000431.4:c.346T>CMANE SELECT
  • NM_001114185.3:c.346T>C
  • NM_001301182.2:c.346T>C
  • NP_000422.1:p.Tyr116His
  • NP_001107657.1:p.Tyr116His
  • NP_001288111.1:p.Tyr116His
  • LRG_156t1:c.346T>C
  • LRG_156:g.11227T>C
  • NC_000012.11:g.110017726T>C
  • NM_000431.1:c.346T>C
  • NM_000431.2:c.346T>C
  • NM_000431.3:c.346T>C
Protein change:
Y116H
Links:
dbSNP: rs104895382
NCBI 1000 Genomes Browser:
rs104895382
Molecular consequence:
  • NM_000431.4:c.346T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114185.3:c.346T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301182.2:c.346T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000279117GeneDxcriteria provided, single submitter
Pathogenic
(Oct 25, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000279117.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The Y116H missense change has been reported previously in individuals with mevalonate kinase deficiency (MKD) or hyperimmunoglobulin D syndrome (Samkari et al., 2010; Levy et al., 2013; Leyva-Vega et al., 2011). It was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. Y116H is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. In addition, missense variants in nearby residues (L117P, I119M) have been reported in the Human Gene Mutation Database in association with MVK-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

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