NM_000264.5(PTCH1):c.3440T>C (p.Phe1147Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 5, 2016
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:: RCV000492461.3

Allele description [Variation Report for NM_000264.5(PTCH1):c.3440T>C (p.Phe1147Ser)]

NM_000264.5(PTCH1):c.3440T>C (p.Phe1147Ser)

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.3440T>C (p.Phe1147Ser)

HGVS:

NC_000009.12:g.95453487A>G
NG_007664.1:g.68479T>C
NM_000264.5:c.3440T>CMANE SELECT
NM_001083602.3:c.3242T>C
NM_001083603.3:c.3437T>C
NM_001083604.3:c.2987T>C
NM_001083605.3:c.2987T>C
NM_001083606.3:c.2987T>C
NM_001083607.3:c.2987T>C
NM_001354918.2:c.3284T>C
NP_000255.2:p.Phe1147Ser
NP_001077071.1:p.Phe1081Ser
NP_001077072.1:p.Phe1146Ser
NP_001077073.1:p.Phe996Ser
NP_001077074.1:p.Phe996Ser
NP_001077075.1:p.Phe996Ser
NP_001077076.1:p.Phe996Ser
NP_001341847.1:p.Phe1095Ser
LRG_515t1:c.3440T>C
LRG_515:g.68479T>C
NC_000009.11:g.98215769A>G
NM_000264.3:c.3440T>C
NR_149061.2:n.4179T>C

Protein change:

F1081S

Links:

dbSNP: rs1131690990

NCBI 1000 Genomes Browser:

rs1131690990

Molecular consequence:

NM_000264.5:c.3440T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001083602.3:c.3242T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001083603.3:c.3437T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001083604.3:c.2987T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001083605.3:c.2987T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001083606.3:c.2987T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001083607.3:c.2987T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354918.2:c.3284T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_149061.2:n.4179T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000581052	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jan 5, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000581052

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jan 5, 2016)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV000581052.6

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

Description

The p.F1147S variant (also known as c.3440T>C), located in coding exon 20 of the PTCH1 gene, results from a T to C substitution at nucleotide position 3440. The phenylalanine at codon 1147 is replaced by serine, an amino acid with highly dissimilar properties. A similar alteration at this same codon, p.F1147C (c.3440T>G), has been reported in a 22 year old male with multiple keratocystic odontogenic tumors, palmar/plantar pits, calcification of the falx cerebri, frontal bossing, and telecanthus. One of this individual's keratocystic odontogenic tumors showed LOH (Sun LS et al. J Dent Res. 2008 Jun;87(6):575-9; Pan S et al. Clin Cancer Res. 2010 Jan 15;16(2):442-50). The p.F1147S variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.4% (greater than 300 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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

Last Updated: May 1, 2024

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