NM_000264.5(PTCH1):c.3395C>T (p.Ser1132Phe) AND Gorlin syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 20, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000800312.10

Allele description

NM_000264.5(PTCH1):c.3395C>T (p.Ser1132Phe)

Gene:

PTCH1:patched 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000264.5(PTCH1):c.3395C>T (p.Ser1132Phe)

HGVS:

NC_000009.12:g.95453532G>A
NG_007664.1:g.68434C>T
NM_000264.5:c.3395C>TMANE SELECT
NM_001083602.3:c.3197C>T
NM_001083603.3:c.3392C>T
NM_001083604.3:c.2942C>T
NM_001083605.3:c.2942C>T
NM_001083606.3:c.2942C>T
NM_001083607.3:c.2942C>T
NM_001354918.2:c.3239C>T
NP_000255.2:p.Ser1132Phe
NP_001077071.1:p.Ser1066Phe
NP_001077072.1:p.Ser1131Phe
NP_001077073.1:p.Ser981Phe
NP_001077074.1:p.Ser981Phe
NP_001077075.1:p.Ser981Phe
NP_001077076.1:p.Ser981Phe
NP_001341847.1:p.Ser1080Phe
LRG_515:g.68434C>T
NC_000009.11:g.98215814G>A
NR_149061.2:n.4134C>T

Protein change:

S1066F

Links:

dbSNP: rs1588528503

NCBI 1000 Genomes Browser:

rs1588528503

Molecular consequence:

NM_000264.5:c.3395C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001083602.3:c.3197C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001083603.3:c.3392C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001083604.3:c.2942C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001083605.3:c.2942C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001083606.3:c.2942C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001083607.3:c.2942C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354918.2:c.3239C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_149061.2:n.4134C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Gorlin syndrome
Synonyms:: Basal cell nevus syndrome
Identifiers:: MONDO: MONDO:0007187; MedGen: C0004779; Orphanet: 377; OMIM: PS109400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000940019	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8840969, 11231326, 23951062, 26544948, 28492532
SCV003804704	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 20, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000940019

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 1, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV003804704

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 20, 2022)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients.

Chidambaram A, Goldstein AM, Gailani MR, Gerrard B, Bale SJ, DiGiovanna JJ, Bale AE, Dean M.

Cancer Res. 1996 Oct 15;56(20):4599-601.

PubMed [citation]

PMID:: 8840969

Coincident PTCH and BRCA1 germline mutations in a patient with nevoid basal cell carcinoma syndrome and familial breast cancer.

Reifenberger J, Arnold N, Kiechle M, Reifenberger G, Hauschild A.

J Invest Dermatol. 2001 Mar;116(3):472-4. No abstract available.

PubMed [citation]

PMID:: 11231326

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000940019.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

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 PTCH1 protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser1132 amino acid residue in PTCH1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8840969, 11231326, 23951062, 26544948). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 646094). This missense change has been observed in individuals with clinical features of basal cell nevus syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1132 of the PTCH1 protein (p.Ser1132Phe).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV003804704.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

_x000D_ Criteria applied: PM5_STR, PS4_MOD, PM2_SUP, PP3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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