NM_000531.6(OTC):c.988A>G (p.Arg330Gly) AND Ornithine carbamoyltransferase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 9, 2021
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:: RCV001857406.4

Allele description [Variation Report for NM_000531.6(OTC):c.988A>G (p.Arg330Gly)]

NM_000531.6(OTC):c.988A>G (p.Arg330Gly)

Gene:

OTC:ornithine transcarbamylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_000531.6(OTC):c.988A>G (p.Arg330Gly)

HGVS:

NC_000023.11:g.38411982A>G
NG_008471.1:g.64500A>G
NM_000531.6:c.988A>GMANE SELECT
NP_000522.3:p.Arg330Gly
LRG_846t1:c.988A>G
LRG_846:g.64500A>G
LRG_846p1:p.Arg330Gly
NC_000023.10:g.38271235A>G
NM_000531.5:c.988A>G
P00480:p.Arg330Gly

Protein change:

R330G

Links:

UniProtKB: P00480#VAR_004939; dbSNP: rs72558478

NCBI 1000 Genomes Browser:

rs72558478

Molecular consequence:

NM_000531.6:c.988A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ornithine carbamoyltransferase deficiency (OTCD)
Synonyms:: ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO; Ornithine transcarbamylase deficiency; OTC deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010703; MedGen: C0268542; Orphanet: 664; OMIM: 311250

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002240986	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 9, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9266388, 10946359, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002240986

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 9, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Identification of 'private' mutations in patients with ornithine transcarbamylase deficiency.

Tuchman M, Morizono H, Rajagopal BS, Plante RJ, Allewell NM.

J Inherit Metab Dis. 1997 Aug;20(4):525-7.

PubMed [citation]

PMID:: 9266388

Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype.

McCullough BA, Yudkoff M, Batshaw ML, Wilson JM, Raper SE, Tuchman M.

Am J Med Genet. 2000 Aug 14;93(4):313-9.

PubMed [citation]

PMID:: 10946359

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002240986.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OTC protein function. This variant has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 9266388, 10946359, Invitae). ClinVar contains an entry for this variant (Variation ID: 97376). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 330 of the OTC protein (p.Arg330Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.

#	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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