NM_002225.5(IVD):c.1243G>A (p.Gly415Ser) AND Isovaleryl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 10, 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:: RCV000634870.10

Allele description [Variation Report for NM_002225.5(IVD):c.1243G>A (p.Gly415Ser)]

NM_002225.5(IVD):c.1243G>A (p.Gly415Ser)

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.1243G>A (p.Gly415Ser)

HGVS:

NC_000015.10:g.40418234G>A
NG_011986.2:g.17750G>A
NM_001159508.3:c.1153G>A
NM_001354597.3:c.1195G>A
NM_001354598.3:c.1138+1872G>A
NM_001354599.3:c.1330G>A
NM_001354600.3:c.1225+1872G>A
NM_001354601.3:c.1138+1872G>A
NM_002225.5:c.1243G>AMANE SELECT
NP_001152980.2:p.Gly385Ser
NP_001341526.1:p.Gly399Ser
NP_001341528.2:p.Gly444Ser
NP_002216.3:p.Gly415Ser
NC_000015.9:g.40710433G>A
NM_002225.3:c.1252G>A

Protein change:

G385S

Links:

dbSNP: rs150855952

NCBI 1000 Genomes Browser:

rs150855952

Molecular consequence:

NM_001354598.3:c.1138+1872G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354600.3:c.1225+1872G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354601.3:c.1138+1872G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001159508.3:c.1153G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354597.3:c.1195G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354599.3:c.1330G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002225.5:c.1243G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000756224	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 10, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002094420	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jan 22, 2019)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000756224

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 10, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002094420

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Jan 22, 2019)

germline

clinical testing

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000756224.5

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 418 of the IVD protein (p.Gly418Ser). This variant is present in population databases (rs150855952, gnomAD 0.01%). This missense change has been observed in individual(s) with a positive newborn screening result for IVD-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 203784). 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 disruptive. 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.

#	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 Natera, Inc., SCV002094420.1

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

Last Updated: Sep 29, 2024

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