NM_000264.5(PTCH1):c.3449+1G>A AND Gorlin syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 10, 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:: RCV000195968.5

Allele description [Variation Report for NM_000264.5(PTCH1):c.3449+1G>A]

NM_000264.5(PTCH1):c.3449+1G>A

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.3449+1G>A

HGVS:

NC_000009.12:g.95453477C>T
NG_007664.1:g.68489G>A
NM_000264.5:c.3449+1G>AMANE SELECT
NM_001083602.3:c.3251+1G>A
NM_001083603.3:c.3446+1G>A
NM_001083604.3:c.2996+1G>A
NM_001083605.3:c.2996+1G>A
NM_001083606.3:c.2996+1G>A
NM_001083607.3:c.2996+1G>A
NM_001354918.2:c.3293+1G>A
LRG_515t1:c.3449+1G>A
LRG_515:g.68489G>A
NC_000009.11:g.98215759C>T
NM_000264.3:c.3449+1G>A

Links:

dbSNP: rs863224442

NCBI 1000 Genomes Browser:

rs863224442

Molecular consequence:

NM_000264.5:c.3449+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001083602.3:c.3251+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001083603.3:c.3446+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001083604.3:c.2996+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001083605.3:c.2996+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001083606.3:c.2996+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001083607.3:c.2996+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354918.2:c.3293+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

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DB045034 TESTI2 Homo sapiens cDNA clone TESTI2033163 5', mRNA sequence
DB045034 TESTI2 Homo sapiens cDNA clone TESTI2033163 5', mRNA sequence
gi|82060433|gnl|dbEST|33693026|dbj| 034.1|

Nucleotide
LOC127269920 [Homo sapiens]
LOC127269920 [Homo sapiens]
Gene ID:127269920

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000253687	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 27561271, 16199547, 16301862, 16419085, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000253687

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2020)

germline

clinical testing

PubMed (5)
[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

Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene.

Kato C, Fujii K, Arai Y, Hatsuse H, Nagao K, Takayama Y, Kameyama K, Fujii K, Miyashita T.

Fam Cancer. 2017 Jan;16(1):131-138. doi: 10.1007/s10689-016-9924-2.

PubMed [citation]

PMID:: 27561271

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

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000253687.5

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

Description

This sequence change affects a donor splice site in intron 20 of the PTCH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of basal cell nevus syndrome (PMID: 27561271). ClinVar contains an entry for this variant (Variation ID: 215985). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 27561271). 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). For these reasons, this variant has been classified as 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: Sep 29, 2024

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