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.
ClinVar Genomic variation as it relates to human health
NM_000264.5(PTCH1):c.735A>G (p.Thr245=)
Germline
Classification
Help
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.
(13)
Help
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.
Benign
13
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000264.5(PTCH1):c.735A>G (p.Thr245=)
Variation ID: 132726 Accession: VCV000132726.31
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 9q22.32 9: 95481960 (GRCh38) [ NCBI UCSC ] 9: 98244242 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 2, 2016 Sep 29, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000264.5:c.735A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000255.2:p.Thr245= synonymous NM_001083603.3:c.732A>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001077072.1:p.Thr244= synonymous NM_001083602.3:c.537A>G NP_001077071.1:p.Thr179= synonymous NM_001083604.3:c.282A>G NP_001077073.1:p.Thr94= synonymous NM_001083605.3:c.282A>G NP_001077074.1:p.Thr94= synonymous NM_001083606.3:c.282A>G NP_001077075.1:p.Thr94= synonymous NM_001083607.3:c.282A>G NP_001077076.1:p.Thr94= synonymous NM_001354918.2:c.735A>G NP_001341847.1:p.Thr245= synonymous NM_001354919.2:c.537A>G NP_001341848.1:p.Thr179= synonymous NR_149061.2:n.1640A>G non-coding transcript variant NC_000009.12:g.95481960T>C NC_000009.11:g.98244242T>C NG_007664.1:g.40006A>G LRG_515:g.40006A>G LRG_515t1:c.735A>G - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000009.12:95481959:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00938 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00938
1000 Genomes Project 30x 0.01015
Trans-Omics for Precision Medicine (TOPMed) 0.02186
The Genome Aggregation Database (gnomAD), exomes 0.02241
The Genome Aggregation Database (gnomAD) 0.02243
Exome Aggregation Consortium (ExAC) 0.02294
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.02760
- 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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| 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
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. |
|---|---|---|---|---|
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000119176.22 | |
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 31, 2021 | RCV000248813.9 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000406017.5 | |
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
May 24, 2016 | RCV000587665.8 | |
| Benign (1) |
criteria provided, single submitter
|
May 4, 2016 | RCV000492478.3 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Mar 31, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002046827.2
First in ClinVar: Jan 03, 2022 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001934853.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
|
Benign
(May 04, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000581009.6
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)
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005272144.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000303362.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(May 24, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696385.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The PTCH1 c.735A>G (p.Thr245Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a … (more)
Variant summary: The PTCH1 c.735A>G (p.Thr245Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant along with 5/5 splice site prediction tools predicting the variant not to have an impact on splicing. This variant was found in 2760/120306 control chromosomes (42 homozygotes) at a frequency of 0.0229415, which is approximately 1339 times the estimated maximal expected allele frequency of a pathogenic PTCH1 variant (0.0000171), suggesting this variant is likely a benign polymorphism. One clinical diagnostic laboratory classified this variant as Benign. Additionally, the variant has been reported in the literature as a polymorphism (Musani_Gene_2013).Taken together and based on the high frequency in the general population, this variant is classified as Benign. (less)
|
|
|
Benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Basal cell nevus syndrome 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000481349.3
First in ClinVar: Dec 06, 2016 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)
|
|
|
Benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Holoprosencephaly 7
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000481348.3
First in ClinVar: Dec 06, 2016 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)
|
|
|
Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Basal cell nevus syndrome 1
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004017146.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Gorlin syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000153908.12
First in ClinVar: Jun 03, 2014 Last updated: Feb 20, 2024 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001806814.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001797402.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001959601.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
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Comment:
Comment:
Variant summary: The PTCH1 c.735A>G (p.Thr245Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant along with 5/5 splice site prediction tools predicting the variant not to have an impact on splicing. This variant was found in 2760/120306 control chromosomes (42 homozygotes) at a frequency of 0.0229415, which is approximately 1339 times the estimated maximal expected allele frequency of a pathogenic PTCH1 variant (0.0000171), suggesting this variant is likely a benign polymorphism. One clinical diagnostic laboratory classified this variant as Benign. Additionally, the variant has been reported in the literature as a polymorphism (Musani_Gene_2013).Taken together and based on the high frequency in the general population, this variant is classified as Benign.
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 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.
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 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.
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. |
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 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.
Comment:
Variant summary: The PTCH1 c.735A>G (p.Thr245Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant along with 5/5 splice site prediction tools predicting the variant not to have an impact on splicing. This variant was found in 2760/120306 control chromosomes (42 homozygotes) at a frequency of 0.0229415, which is approximately 1339 times the estimated maximal expected allele frequency of a pathogenic PTCH1 variant (0.0000171), suggesting this variant is likely a benign polymorphism. One clinical diagnostic laboratory classified this variant as Benign. Additionally, the variant has been reported in the literature as a polymorphism (Musani_Gene_2013).Taken together and based on the high frequency in the general population, this variant is classified as Benign.
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 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.
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 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| PTCH1 gene polymorphisms in ovarian tumors: potential protective role of c.3944T allele. | Musani V | Gene | 2013 | PMID: 23313819 |
Text-mined citations for rs1805154 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.