NM_054012.4(ASS1):c.805G>A (p.Val269Met) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Jun 22, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000412912.2

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

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

Gene:
ASS1:argininosuccinate synthase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_054012.4(ASS1):c.805G>A (p.Val269Met)
HGVS:
  • 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:
V269M
Links:
UniProtKB: P00966#VAR_015901; dbSNP: rs370595480
NCBI 1000 Genomes Browser:
rs370595480
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]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000225474EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Jun 22, 2018)
germlineclinical testing

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

Citation Link,

SCV000490413GeneDxcriteria provided, single submitter
Pathogenic
(May 7, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing

Citations

PubMed

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]
PMID:
12815590

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000225474.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From GeneDx, SCV000490413.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The V269M missense variant in the ASS1 gene has been reported previously in association with classic citrullinemia (Gao et al., 2003). It was hypothesized that the V269M variant may affect the tertiary and/or quaternary structure of the protein (Gao et al., 2003). Further, V269M occurs at a position that is conserved across mammals, in silico analysis predicts this variant is probably damaging to the protein structure/function, and missense variants in nearby residues (R265C, R265H, E270Q, R272C) have also been reported in the Human Gene Mutation Database in association with citrullinaemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret V269M to be pathogenic mutations.

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

Last Updated: Aug 27, 2021

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