NM_000264.5(PTCH1):c.585-1G>C AND Gorlin syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 2020
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:: RCV000558322.6

Allele description [Variation Report for NM_000264.5(PTCH1):c.585-1G>C]

NM_000264.5(PTCH1):c.585-1G>C

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.585-1G>C

HGVS:

NC_000009.12:g.95482204C>G
NG_007664.1:g.39762G>C
NM_000264.5:c.585-1G>CMANE SELECT
NM_001083602.3:c.387-1G>C
NM_001083603.3:c.582-1G>C
NM_001083604.3:c.132-1G>C
NM_001083605.3:c.132-1G>C
NM_001083606.3:c.132-1G>C
NM_001083607.3:c.132-1G>C
NM_001354918.2:c.585-1G>C
NM_001354919.2:c.387-1G>C
LRG_515t1:c.585-1G>C
LRG_515:g.39762G>C
NC_000009.11:g.98244486C>G
NM_000264.3:c.585-1G>C

Links:

dbSNP: rs1057520590

NCBI 1000 Genomes Browser:

rs1057520590

Molecular consequence:

NM_000264.5:c.585-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001083602.3:c.387-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001083603.3:c.582-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001083604.3:c.132-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001083605.3:c.132-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001083606.3:c.132-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001083607.3:c.132-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354918.2:c.585-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354919.2:c.387-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Gorlin syndrome
Synonyms:: Gorlin-Goltz Syndrome; Multiple Basal Cell Nevi, Odontogenic Keratocysts, And Skeletal Anomalies; Fifth Phacomatosis; See all synonyms [MedGen]
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
SCV000623050	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 16301862, 16419085, 22952776, 24816767, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000623050

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2020)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Clinical testing for the nevoid basal cell carcinoma syndrome in a DNA diagnostic laboratory.

Klein RD, Dykas DJ, Bale AE.

Genet Med. 2005 Nov-Dec;7(9):611-9.

PubMed [citation]

PMID:: 16301862

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000623050.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PTCH1 are known to be pathogenic (PMID: 16301862, 16419085). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individuals with basal cell nevus syndrome (PMID: 22952776, 24816767, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the PTCH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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: Feb 28, 2024

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