ClinVar Genomic variation as it relates to human health
NM_017837.4(PIGV):c.614A>G (p.Asn205Ser)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Likely pathogenic(2); Uncertain significance(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_017837.4(PIGV):c.614A>G (p.Asn205Ser)
Variation ID: 421662 Accession: VCV000421662.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.11 1: 26794648 (GRCh38) [ NCBI UCSC ] 1: 27121139 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 27, 2017 Apr 15, 2024 Aug 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_017837.4:c.614A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060307.2:p.Asn205Ser missense NM_001202554.2:c.614A>G NP_001189483.1:p.Asn205Ser missense NM_001374478.1:c.614A>G NP_001361407.1:p.Asn205Ser missense NM_001374480.1:c.614A>G NP_001361409.1:p.Asn205Ser missense NM_001374481.1:c.614A>G NP_001361410.1:p.Asn205Ser missense NM_001374482.1:c.614A>G NP_001361411.1:p.Asn205Ser missense NM_001374483.1:c.233A>G NP_001361412.1:p.Asn78Ser missense NM_001374484.1:c.173-186A>G intron variant NM_001374485.1:c.173-186A>G intron variant NM_001374486.1:c.79-2915A>G intron variant NR_164651.1:n.1112A>G non-coding transcript variant NC_000001.11:g.26794648A>G NC_000001.10:g.27121139A>G NG_028133.1:g.11686A>G - Protein change
- N205S, N78S
- Other names
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- Canonical SPDI
- NC_000001.11:26794647:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PIGV | - | - |
GRCh38 GRCh37 |
328 | 337 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Aug 24, 2023 | RCV000482776.23 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001097857.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 15, 2018 | RCV001267017.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001254179.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Jan 15, 2018)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV001445198.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Caucasian/English/Norwegian/German/European
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Likely pathogenic
(Jul 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000570944.5
First in ClinVar: Apr 27, 2017 Last updated: Jul 16, 2023 |
Comment:
Reported as a pathogenic variant in a cohort of individuals undergoing whole exome seqeuncing for preconception carrier screening (Capalbo et al., 2019); Observed with another … (more)
Reported as a pathogenic variant in a cohort of individuals undergoing whole exome seqeuncing for preconception carrier screening (Capalbo et al., 2019); Observed with another likely pathogenic variant in a patient with GPI-deficiency-associated epilepsy and neurodevelopmental impairment in published literature (Bayat et al., 2022); however, it is unclear whether the variants are on the same allele (in cis) or on opposite alleles (in trans); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 35080266) (less)
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Uncertain significance
(Aug 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002112749.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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 PIGV protein function. ClinVar contains an entry for this variant (Variation ID: 421662). This variant has not been reported in the literature in individuals affected with PIGV-related conditions. This variant is present in population databases (rs766452597, gnomAD 0.005%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 205 of the PIGV protein (p.Asn205Ser). (less)
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Likely pathogenic
(Aug 01, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000891818.22
First in ClinVar: Mar 31, 2019 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs766452597 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.