NM_000531.6(OTC):c.422G>A (p.Arg141Gln) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 9, 2020
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:: RCV000083434.7

Allele description [Variation Report for NM_000531.6(OTC):c.422G>A (p.Arg141Gln)]

NM_000531.6(OTC):c.422G>A (p.Arg141Gln)

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.422G>A (p.Arg141Gln)

Other names:

R109Q

HGVS:

NC_000023.11:g.38401310G>A
NG_008471.1:g.53828G>A
NM_000531.6:c.422G>AMANE SELECT
NP_000522.3:p.Arg141Gln
LRG_846t1:c.422G>A
LRG_846:g.53828G>A
LRG_846p1:p.Arg141Gln
NC_000023.10:g.38260563G>A
NM_000531.5:c.422G>A
P00480:p.Arg141Gln

Protein change:

R141Q; ARG109GLN

Links:

UniProtKB: P00480#VAR_004879; OMIM: 300461.0002; dbSNP: rs68026851

NCBI 1000 Genomes Browser:

rs68026851

Molecular consequence:

NM_000531.6:c.422G>A - 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
SCV000115520	GenMed Metabolism Lab	no assertion criteria provided	pathogenic	unknown	not provided	PubMed (1) [See all records that cite this PMID]
SCV000230943	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (May 19, 2015)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11102556, 17044854, 3170748 Citation Link,
SCV001802043	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 9, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000115520

GenMed Metabolism Lab

no assertion criteria provided

pathogenic

unknown

not provided

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

SCV000230943

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(May 19, 2015)

germline

clinical testing

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

Citation Link,

SCV001802043

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 9, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	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
not provided	unknown	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Expression of wild-type and mutant human ornithine transcarbamylase genes in Chinese hamster ovary cells and lack of dominant negative effect of R141Q and R40H mutants.

Augustin L, Mavinakere M, Morizono H, Tuchman M.

Pediatr Res. 2000 Dec;48(6):842-6.

PubMed [citation]

PMID:: 11102556

Mutational spectrum and linkage disequilibrium patterns at the ornithine transcarbamylase gene (OTC).

Azevedo L, Soares PA, Quental R, Vilarinho L, Teles EL, Martins E, Diogo L, Garcia P, Cenni B, Wermuth B, Amorim A.

Ann Hum Genet. 2006 Nov;70(Pt 6):797-801.

PubMed [citation]

PMID:: 17044854

See all PubMed Citations (3)

Details of each submission

From GenMed Metabolism Lab, SCV000115520.1

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

Description

Converted during submission to Pathogenic.

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

From Eurofins Ntd Llc (ga), SCV000230943.5

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

#	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

From GeneDx, SCV001802043.1

#	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 that R141Q is associated with significantly reduced OTC activity compared to wild-type (Lee et al., 1989; Augustin et al., 2000).; Not observed in large population cohorts (Lek et al., 2016); 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: 33272297, 31589614, 28324312, 8985493, 8830175, 17044854, 1757964, 3170748, 1627356, 2556444, 11102556, 30175132)

#	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

Last Updated: Feb 14, 2024

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