NM_001875.4(CPS1):c.3643A>G (p.Ile1215Val) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Mar 23, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000224815.2

Allele description [Variation Report for NM_001875.4(CPS1):c.3643A>G (p.Ile1215Val)]

NM_001875.4(CPS1):c.3643A>G (p.Ile1215Val)

Gene:
CPS1:carbamoyl-phosphate synthase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q34
Genomic location:
Preferred name:
NM_001875.4(CPS1):c.3643A>G (p.Ile1215Val)
HGVS:
  • NC_000002.12:g.210656609A>G
  • NG_008285.1:g.183925A>G
  • NM_001875.4:c.3643A>G
  • NP_001866.2:p.Ile1215Val
  • LRG_336t1:c.3643A>G
  • LRG_336:g.183925A>G
  • LRG_336p1:p.Ile1215Val
  • NC_000002.11:g.211521333A>G
  • P31327:p.Ile1215Val
Protein change:
I1215V
Links:
UniProtKB: P31327#VAR_063574; dbSNP: rs141373204
NCBI 1000 Genomes Browser:
rs141373204
Molecular consequence:
  • NM_001875.4:c.3643A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000281406Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinicscriteria provided, single submitter
Uncertain Significance
(Jan 21, 2016)
germlineclinical testing

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

SCV000575297Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Uncertain significance
(Jan 31, 2017)
germlineclinical testing

Citation Link,

SCV000577569GeneDxcriteria provided, single submitter
Uncertain significance
(Mar 23, 2018)
germlineclinical testing

Citation Link,

SCV000855927EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Aug 1, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000281406.1

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

Description

Converted during submission to Uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot provided0.001906not providednot provided

From Praxis fuer Humangenetik Tuebingen, SCV000575297.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000577569.4

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

Description

The I1215V variant has been reported previously in a patient with carbamoylphosphate synthetase I (CPS1) deficiency who also harbored a second variant in the CPS1 gene (Kurokawa et al. 2007). The I1215V variant is observed in 31/11564 (0.27%) alleles from individuals of Latino background, in the ExAC dataset including a homozygous individual (Lek et al., 2016). The I1215V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine and Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000855927.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Apr 17, 2019

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