ClinVar Genomic variation as it relates to human health
NM_000264.5(PTCH1):c.2558A>G (p.Gln853Arg)
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.
Uncertain significance(3); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000264.5(PTCH1):c.2558A>G (p.Gln853Arg)
Variation ID: 135096 Accession: VCV000135096.15
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 9q22.32 9: 95467118 (GRCh38) [ NCBI UCSC ] 9: 98229400 (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 Jun 9, 2014 May 1, 2024 Jan 18, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000264.5:c.2558A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000255.2:p.Gln853Arg missense NM_001083603.3:c.2555A>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001077072.1:p.Gln852Arg missense NM_001083602.3:c.2360A>G NP_001077071.1:p.Gln787Arg missense NM_001083604.3:c.2105A>G NP_001077073.1:p.Gln702Arg missense NM_001083605.3:c.2105A>G NP_001077074.1:p.Gln702Arg missense NM_001083606.3:c.2105A>G NP_001077075.1:p.Gln702Arg missense NM_001083607.3:c.2105A>G NP_001077076.1:p.Gln702Arg missense NM_001354918.2:c.2402A>G NP_001341847.1:p.Gln801Arg missense NR_038982.1:n.379T>C non-coding transcript variant NR_149061.2:n.3297A>G non-coding transcript variant NC_000009.12:g.95467118T>C NC_000009.11:g.98229400T>C NG_007664.1:g.54848A>G LRG_515:g.54848A>G LRG_515t1:c.2558A>G - Protein change
- Q787R, Q853R, Q852R, Q702R, Q801R
- Other names
- -
- Canonical SPDI
- NC_000009.12:95467117:T:C
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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 |
3924 | 5100 | |
LOC100507346 | - | - | - | GRCh38 | - | 852 |
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. |
---|---|---|---|---|
not provided (1) |
no classification provided
|
Sep 19, 2013 | RCV000121887.1 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 18, 2024 | RCV000462194.11 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Jan 17, 2023 | RCV002255299.6 | |
Uncertain significance (1) |
criteria provided, single submitter
|
May 28, 2023 | RCV003126502.2 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Jan 18, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Gorlin syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000549087.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 853 of the PTCH1 protein (p.Gln853Arg). … (more)
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 853 of the PTCH1 protein (p.Gln853Arg). This variant is present in population databases (rs587778628, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 135096). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. (less)
|
|
Uncertain significance
(Aug 23, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002526855.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The PTCH1 c.2558A>G (p.Q853R) variant has been reported in 1 individual in an ancestrally-diverse healthy population (PMID: 24728327). This variant observed in 3/113560 chromosomes in … (more)
The PTCH1 c.2558A>G (p.Q853R) variant has been reported in 1 individual in an ancestrally-diverse healthy population (PMID: 24728327). This variant observed in 3/113560 chromosomes in the Non-Finnish European population according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 135096). Functional studies have not been performed, and in silico predictions of the variant's effect on protein function are inconclusive. The overall evidence is insufficient to meet ACMG/AMP criteria for classifying it as benign or pathogenic. In summary, the clinical significance of this variant is currently uncertain. (less)
|
|
|
Uncertain significance
(May 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV003803312.2
First in ClinVar: Feb 18, 2023 Last updated: Jun 03, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in healthy individuals undergoing whole genome sequencing (Bodian et al., 2014); This variant is associated with the following publications: (PMID: 24728327, 8906794) (less)
|
|
Likely benign
(Jan 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002741140.3
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely 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)
|
|
not provided
(Sep 19, 2013)
|
no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000086090.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
|
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
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Text-mined citations for rs587778628 ...
HelpRecord last updated May 08, 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.