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NM_000264.5(PTCH1):c.3394T>A (p.Ser1132Thr) AND Gorlin syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 25, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001035959.7

Allele description [Variation Report for NM_000264.5(PTCH1):c.3394T>A (p.Ser1132Thr)]

NM_000264.5(PTCH1):c.3394T>A (p.Ser1132Thr)

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.3394T>A (p.Ser1132Thr)
HGVS:
  • NC_000009.12:g.95453533A>T
  • NG_007664.1:g.68433T>A
  • NM_000264.5:c.3394T>AMANE SELECT
  • NM_001083602.3:c.3196T>A
  • NM_001083603.3:c.3391T>A
  • NM_001083604.3:c.2941T>A
  • NM_001083605.3:c.2941T>A
  • NM_001083606.3:c.2941T>A
  • NM_001083607.3:c.2941T>A
  • NM_001354918.2:c.3238T>A
  • NP_000255.2:p.Ser1132Thr
  • NP_001077071.1:p.Ser1066Thr
  • NP_001077072.1:p.Ser1131Thr
  • NP_001077073.1:p.Ser981Thr
  • NP_001077074.1:p.Ser981Thr
  • NP_001077075.1:p.Ser981Thr
  • NP_001077076.1:p.Ser981Thr
  • NP_001341847.1:p.Ser1080Thr
  • LRG_515t1:c.3394T>A
  • LRG_515:g.68433T>A
  • NC_000009.11:g.98215815A>T
  • NM_000264.3:c.3394T>A
  • NR_149061.2:n.4133T>A
Protein change:
S1066T
Links:
dbSNP: rs878853856
NCBI 1000 Genomes Browser:
rs878853856
Molecular consequence:
  • NM_000264.5:c.3394T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083602.3:c.3196T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083603.3:c.3391T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083604.3:c.2941T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083605.3:c.2941T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083606.3:c.2941T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083607.3:c.2941T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354918.2:c.3238T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149061.2:n.4133T>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001199299Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 25, 2019) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Integrated genotypic analysis of hedgehog-related genes identifies subgroups of keratocystic odontogenic tumor with distinct clinicopathological features.

Shimada Y, Katsube K, Kabasawa Y, Morita K, Omura K, Yamaguchi A, Sakamoto K.

PLoS One. 2013;8(8):e70995. doi: 10.1371/journal.pone.0070995.

PubMed [citation]
PMID:
23951062
PMCID:
PMC3737235
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001199299.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

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. 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: 11231326, 23951062, 8840969). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PTCH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 1132 of the PTCH1 protein (p.Ser1132Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024