NM_000431.4(MVK):c.803T>C (p.Ile268Thr) AND not provided

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

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Jun 20, 2023
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:: RCV000218157.26

Allele description

NM_000431.4(MVK):c.803T>C (p.Ile268Thr)

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.803T>C (p.Ile268Thr)

HGVS:

NC_000012.12:g.109591275T>C
NG_007702.1:g.22581T>C
NM_000431.4:c.803T>CMANE SELECT
NM_001114185.3:c.803T>C
NM_001301182.2:c.647T>C
NP_000422.1:p.Ile268Thr
NP_001107657.1:p.Ile268Thr
NP_001288111.1:p.Ile216Thr
LRG_156t1:c.803T>C
LRG_156:g.22581T>C
LRG_156p1:p.Ile268Thr
NC_000012.11:g.110029080T>C
NM_000431.1:c.803T>C
NM_000431.2:c.803T>C
NM_000431.3:c.803T>C
NM_001114185.1:c.803T>C
NM_001301182.1:c.647T>C
Q03426:p.Ile268Thr

Protein change:

I216T; ILE268THR

Links:

UniProtKB: Q03426#VAR_004024; OMIM: 251170.0004; dbSNP: rs104895304

NCBI 1000 Genomes Browser:

rs104895304

Molecular consequence:

NM_000431.4:c.803T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001114185.3:c.803T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001301182.2:c.647T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000279122	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 20, 2023)	germline	clinical testing	Citation Link,
SCV001746157	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jan 1, 2023)	germline	clinical testing	Citation Link,
SCV001808261	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001930874	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001956678	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001975859	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV004226634	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 15, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 27142780, 28359055, 31474985, 32060250, 33917151, 34145613, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Natural history of mevalonate kinase deficiency: a literature review.

Zhang S.

Pediatr Rheumatol Online J. 2016 May 4;14(1):30. doi: 10.1186/s12969-016-0091-7. Review.

PubMed [citation]

PMID:: 27142780
PMCID:: PMC4855321

Lack of Prenylated Proteins, Autophagy Impairment and Apoptosis in SH-SY5Y Neuronal Cell Model of Mevalonate Kinase Deficiency.

Tricarico PM, Romeo A, Gratton R, Crovella S, Celsi F.

Cell Physiol Biochem. 2017;41(4):1649-1660. doi: 10.1159/000471235. Epub 2017 Mar 28.

PubMed [citation]

PMID:: 28359055

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000279122.12

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

Description

Published functional studies demonstrate decreased mevalonate kinase activity as compared with wild type (Houten et al., 1999); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24088041, 11313768, 15536479, 29290516, 34525209, 34145613, 32060250, 23692791, 21425920, 10369262, 10417275, 11313769, 25897835, 24470648, 26116953, 26990548, 18839211, 10896296, 24084495, 31028937, 31474985, 31589614, 35753512, 19011501, 10369261)

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

From CeGaT Center for Human Genetics Tuebingen, SCV001746157.14

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

Description

MVK: PM3:Very Strong, PM2, PS3:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001808261.1

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

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001930874.1

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

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001956678.1

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

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001975859.1

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

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226634.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

PP3, PP4, PM2, PM3, PS3, PS4

#	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		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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