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:

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

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

MVK:mevalonate kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000431.4(MVK):c.346T>C (p.Tyr116His)
  • 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:
dbSNP: rs104895382
NCBI 1000 Genomes Browser:
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]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000279117GeneDxcriteria provided, single submitter
(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


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.

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

Last Updated: Oct 8, 2021

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