ClinVar Genomic variation as it relates to human health
NM_000264.5(PTCH1):c.3947A>G (p.Tyr1316Cys)
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(1); Benign(3); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000264.5(PTCH1):c.3947A>G (p.Tyr1316Cys)
Variation ID: 132723 Accession: VCV000132723.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q22.32 9: 95447309 (GRCh38) [ NCBI UCSC ] 9: 98209591 (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 Feb 12, 2016 Oct 20, 2024 Jun 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000264.5:c.3947A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000255.2:p.Tyr1316Cys missense NM_001083603.3:c.3944A>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001077072.1:p.Tyr1315Cys missense NM_001083602.3:c.3749A>G NP_001077071.1:p.Tyr1250Cys missense NM_001083604.3:c.3494A>G NP_001077073.1:p.Tyr1165Cys missense NM_001083605.3:c.3494A>G NP_001077074.1:p.Tyr1165Cys missense NM_001083606.3:c.3494A>G NP_001077075.1:p.Tyr1165Cys missense NM_001083607.3:c.3494A>G NP_001077076.1:p.Tyr1165Cys missense NM_001354918.2:c.3791A>G NP_001341847.1:p.Tyr1264Cys missense NR_149061.2:n.4686A>G non-coding transcript variant NC_000009.12:g.95447309T>C NC_000009.11:g.98209591T>C NG_007664.1:g.74657A>G LRG_515:g.74657A>G LRG_515t1:c.3947A>G - Protein change
- Y1250C, Y1316C, Y1165C, Y1264C, Y1315C
- Other names
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- Canonical SPDI
- NC_000009.12:95447308:T:C
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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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loss_of_function_variant; Sequence Ontology [ SO:0002054]
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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
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The frequency of the allele represented by this VCV record.
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Trans-Omics for Precision Medicine (TOPMed) 0.00049
The Genome Aggregation Database (gnomAD) 0.00051
The Genome Aggregation Database (gnomAD), exomes 0.00055
Exome Aggregation Consortium (ExAC) 0.00064
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00072
- Links
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
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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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PTCH1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4019 | 5230 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2013 | RCV000207364.1 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 17, 2021 | RCV000492441.4 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2024 | RCV000588636.14 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV001166719.4 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV001084106.10 | |
PTCH1-related disorder
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Likely benign (1) |
no assertion criteria provided
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Oct 9, 2020 | RCV004551169.2 |
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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Likely pathogenic
(Jan 01, 2013)
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criteria provided, single submitter
Method: clinical testing, research
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Irido-corneo-trabecular dysgenesis
Rieger anomaly (Autosomal dominant inheritance)
Affected status: yes
Allele origin:
inherited,
maternal
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Paul Sabatier University EA-4555, Paul Sabatier University
Accession: SCV000259154.2
First in ClinVar: Feb 12, 2016 Last updated: Feb 12, 2016 |
Comment:
rare variant, functional studies demonstrating is deleterious effect on protein.
Observation 1:
Clinical Features:
Peters anomaly (present)
Family history: yes
Tissue: DNA extracted from blood samples
Segregation observed: yes
Observation 2:
Result:
mutant mRNA does not rescue morphant phenotypes to the extent of WT mRNA
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Likely benign
(Aug 31, 2016)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696383.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The PTCH1 c.3947A>G (p.Tyr1316Cys) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a damaging outcome for this variant … (more)
Variant summary: The PTCH1 c.3947A>G (p.Tyr1316Cys) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 74/115500 control chromosomes from ExAC at a frequency of 0.0006407, which is approximately 37 times the estimated maximal expected allele frequency of a pathogenic PTCH1 variant (0.0000171), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory in ClinVar has classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. One internal sample with this variant also carries FLCN c.584delG (p.G195fs*28). Taken together, this variant is currently classified as likely benign. (less)
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Likely benign
(Feb 17, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002526922.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Gorlin syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000153902.14
First in ClinVar: Jun 03, 2014 Last updated: Feb 20, 2024 |
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Likely benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Holoprosencephaly 7
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001329122.1
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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Basal cell nevus syndrome 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001329123.1
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Jul 06, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000581032.6
First in ClinVar: Jul 01, 2017 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(Jun 01, 2024)
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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: SCV001155668.15
First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024 |
Comment:
PTCH1: BS1
Number of individuals with the variant: 1
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Likely benign
(Oct 09, 2020)
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no assertion criteria provided
Method: clinical testing
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PTCH1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004777062.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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loss_of_function_variant
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Paul Sabatier University EA-4555, Paul Sabatier University
Accession: SCV000259154.2
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network. | Chassaing N | Genome research | 2016 | PMID: 26893459 |
Location of gene for Gorlin syndrome. | Farndon PA | Lancet (London, England) | 1992 | PMID: 1347096 |
Text-mined citations for rs147067171 ...
HelpRecord last updated Nov 03, 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.