NM_000531.6(OTC):c.188T>C (p.Leu63Pro) AND Ornithine carbamoyltransferase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 10, 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:: RCV001854455.4

Allele description [Variation Report for NM_000531.6(OTC):c.188T>C (p.Leu63Pro)]

NM_000531.6(OTC):c.188T>C (p.Leu63Pro)

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.188T>C (p.Leu63Pro)

HGVS:

NC_000023.11:g.38367401T>C
NG_008471.1:g.19919T>C
NM_000531.6:c.188T>CMANE SELECT
NP_000522.3:p.Leu63Pro
LRG_846t1:c.188T>C
LRG_846:g.19919T>C
LRG_846p1:p.Leu63Pro
NC_000023.10:g.38226654T>C
NM_000531.5:c.188T>C
P00480:p.Leu63Pro

Protein change:

L63P

Links:

UniProtKB: P00480#VAR_004857; dbSNP: rs72554324

NCBI 1000 Genomes Browser:

rs72554324

Molecular consequence:

NM_000531.6:c.188T>C - 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
SCV002138863	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 10, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9143919, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002138863

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 10, 2021)

germline

clinical testing

PubMed (2)
[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

Ornithine transcarbamylase deficiency: ten new mutations and high proportion of de novo mutations in heterozygous females.

Oppliger Leibundgut E, Liechti-Gallati S, Colombo JP, Wermuth B.

Hum Mutat. 1997;9(5):409-11. No abstract available.

PubMed [citation]

PMID:: 9143919

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, SCV002138863.3

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

Description

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. 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: 9143919). ClinVar contains an entry for this variant (Variation ID: 97129). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 63 of the OTC protein (p.Leu63Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.

#	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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