NM_002225.5(IVD):c.890C>T (p.Ala297Val) AND Isovaleryl-CoA dehydrogenase deficiency

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

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Jan 1, 2024
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:: RCV000412245.10

Allele description

NM_002225.5(IVD):c.890C>T (p.Ala297Val)

Gene:

IVD:isovaleryl-CoA dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q15.1

Genomic location:

Preferred name:

NM_002225.5(IVD):c.890C>T (p.Ala297Val)

HGVS:

NC_000015.10:g.40415412C>T
NG_011986.2:g.14928C>T
NM_001159508.3:c.800C>T
NM_001354597.3:c.842C>T
NM_001354598.3:c.890C>T
NM_001354599.3:c.977C>T
NM_001354600.3:c.977C>T
NM_001354601.3:c.890C>T
NM_002225.5:c.890C>TMANE SELECT
NP_001152980.2:p.Ala267Val
NP_001341526.1:p.Ala281Val
NP_001341527.2:p.Ala297Val
NP_001341528.2:p.Ala326Val
NP_001341529.2:p.Ala326Val
NP_001341530.2:p.Ala297Val
NP_002216.3:p.Ala297Val
NC_000015.9:g.40707611C>T
NM_002225.3:c.899C>T
NR_148925.2:n.1302C>T

Protein change:

A267V

Links:

dbSNP: rs796051983

NCBI 1000 Genomes Browser:

rs796051983

Molecular consequence:

NM_001159508.3:c.800C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354597.3:c.842C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354598.3:c.890C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354599.3:c.977C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354600.3:c.977C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354601.3:c.890C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002225.5:c.890C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_148925.2:n.1302C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Isovaleryl-CoA dehydrogenase deficiency (IVA)
Synonyms:: Isovaleric acid CoA dehydrogenase deficiency; Isovaleric acidemia; Isovaleryl CoA carboxylase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009475; MedGen: C0268575; Orphanet: 33; OMIM: 243500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000486747	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Aug 2, 2016)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV001424444	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003442829	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25220015, 31707166, 35782626, 28492532
SCV003831777	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 19, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004198024	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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

Citations

PubMed

Phenotypic and genotypic spectrum of Turkish patients with isovaleric acidemia.

Ozgul RK, Karaca M, Kilic M, Kucuk O, Yucel-Yilmaz D, Unal O, Hismi B, Aliefendioglu D, Sivri S, Tokatli A, Coskun T, Dursun A.

Eur J Med Genet. 2014 Oct;57(10):596-601. doi: 10.1016/j.ejmg.2014.08.006. Epub 2014 Sep 8.

PubMed [citation]

PMID:: 25220015

Molecular analysis using targeted next generation DNA sequencing and clinical spectrum of Mexican patients with isovaleric acidemia.

Ibarra-González I, Fernández-Lainez C, Guillén-López S, López-Mejía L, Belmont-Matínez L, Sokolsky TD, Amin VR, Kitchener RL, Vela-Amieva M, Naylor EW, Bhattacharjee A.

Clin Chim Acta. 2020 Feb;501:216-221. doi: 10.1016/j.cca.2019.10.041. Epub 2019 Nov 9.

PubMed [citation]

PMID:: 31707166

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000486747.2

#	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

From Centogene AG - the Rare Disease Company, SCV001424444.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV003442829.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 300 of the IVD protein (p.Ala300Val). This variant is present in population databases (rs796051983, gnomAD 0.006%). This missense change has been observed in individual(s) with isovaleric acidemia (PMID: 25220015, 31707166, 35782626). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.890C>T p.Ala268Val; c.890C >T; p.Ala297Val . ClinVar contains an entry for this variant (Variation ID: 203792). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.

#	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 Revvity Omics, Revvity, SCV003831777.2

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004198024.2

#	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: Jun 17, 2024

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