NM_054012.4(ASS1):c.805G>A (p.Val269Met) AND Citrullinemia

Clinical significance:Pathogenic (Last evaluated: Oct 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_054012.4(ASS1):c.805G>A (p.Val269Met)]

NM_054012.4(ASS1):c.805G>A (p.Val269Met)

ASS1:argininosuccinate synthase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_054012.4(ASS1):c.805G>A (p.Val269Met)
  • NC_000009.12:g.130480416G>A
  • NG_011542.1:g.40710G>A
  • NM_000050.4:c.805G>A
  • NM_054012.4:c.805G>AMANE SELECT
  • NP_000041.2:p.Val269Met
  • NP_446464.1:p.Val269Met
  • NC_000009.11:g.133355803G>A
  • P00966:p.Val269Met
Protein change:
UniProtKB: P00966#VAR_015901; dbSNP: rs370595480
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000050.4:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_054012.4:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]


Citrullinemia (CTNL1)
MONDO: MONDO:0015991; MedGen: C0175683

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000957991Invitaecriteria provided, single submitter
(Oct 8, 2020)
germlineclinical testing

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

Summary from all submissions

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



Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients.

Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, et al.

Hum Mutat. 2003 Jul;22(1):24-34.

PubMed [citation]

Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1).

Häberle J, Pauli S, Schmidt E, Schulze-Eilfing B, Berning C, Koch HG.

Mol Genet Metab. 2003 Nov;80(3):302-6.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000957991.3

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


This sequence change replaces valine with methionine at codon 269 of the ASS1 protein (p.Val269Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs370595480, ExAC 0.01%). This variant has been observed on the opposite chromosome (in trans) from a variant in an individual affected with mild citrullinemia type 1 (PMID: 12815590) and has also been reported in other unrelated mildly affected individuals (PMID: 14680976, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 193968). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Aug 27, 2021

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