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NM_000531.6(OTC):c.1019C>T (p.Ser340Phe) AND Ornithine carbamoyltransferase deficiency

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Aug 31, 2022
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:
RCV001376924.8

Allele description [Variation Report for NM_000531.6(OTC):c.1019C>T (p.Ser340Phe)]

NM_000531.6(OTC):c.1019C>T (p.Ser340Phe)

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.1019C>T (p.Ser340Phe)
HGVS:
  • NC_000023.11:g.38421036C>T
  • NG_008471.1:g.73554C>T
  • NM_000531.6:c.1019C>TMANE SELECT
  • NP_000522.3:p.Ser340Phe
  • LRG_846t1:c.1019C>T
  • LRG_846:g.73554C>T
  • LRG_846p1:p.Ser340Phe
  • NC_000023.10:g.38280289C>T
  • NM_000531.5:c.1019C>T
Protein change:
S340F
Links:
dbSNP: rs1569282905
NCBI 1000 Genomes Browser:
rs1569282905
Molecular consequence:
  • NM_000531.6:c.1019C>T - 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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001574124Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Aug 31, 2022)
germlineclinical testing

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

SCV002033202Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Nov 7, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Clinical and molecular characteristics of 69 Chinese patients with ornithine transcarbamylase deficiency.

Lu D, Han F, Qiu W, Zhang H, Ye J, Liang L, Wang Y, Ji W, Zhan X, Gu X, Han L.

Orphanet J Rare Dis. 2020 Dec 3;15(1):340. doi: 10.1186/s13023-020-01606-2.

PubMed [citation]
PMID:
33272297
PMCID:
PMC7712605
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001574124.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant disrupts the p.Ser340 amino acid residue in OTC. Other variant(s) that disrupt this residue have been observed in individuals with OTC-related conditions (PMID: 9143919), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 618259). This missense change has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 33272297; Invitae; external communication). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 340 of the OTC protein (p.Ser340Phe).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV002033202.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024