NM_000264.5(PTCH1):c.3364_3365del (p.Met1122fs) AND Gorlin syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 26, 2022
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:: RCV000466769.7

Allele description [Variation Report for NM_000264.5(PTCH1):c.3364_3365del (p.Met1122fs)]

NM_000264.5(PTCH1):c.3364_3365del (p.Met1122fs)

Gene:

PTCH1:patched 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000264.5(PTCH1):c.3364_3365del (p.Met1122fs)

HGVS:

NC_000009.12:g.95453562_95453563del
NG_007664.1:g.68403_68404del
NM_000264.5:c.3364_3365delMANE SELECT
NM_001083602.3:c.3166_3167del
NM_001083603.3:c.3361_3362del
NM_001083604.3:c.2911_2912del
NM_001083605.3:c.2911_2912del
NM_001083606.3:c.2911_2912del
NM_001083607.3:c.2911_2912del
NM_001354918.2:c.3208_3209del
NP_000255.2:p.Met1122fs
NP_001077071.1:p.Met1056fs
NP_001077072.1:p.Met1121fs
NP_001077073.1:p.Met971fs
NP_001077074.1:p.Met971fs
NP_001077075.1:p.Met971fs
NP_001077076.1:p.Met971fs
NP_001341847.1:p.Met1070fs
LRG_515t1:c.3364_3365del
LRG_515:g.68403_68404del
NC_000009.11:g.98215844_98215845del
NM_000264.3:c.3364_3365delAT
NR_149061.2:n.4103_4104del

Protein change:

M1056fs

Links:

dbSNP: rs1060502273

NCBI 1000 Genomes Browser:

rs1060502273

Molecular consequence:

NM_000264.5:c.3364_3365del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001083602.3:c.3166_3167del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001083603.3:c.3361_3362del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001083604.3:c.2911_2912del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001083605.3:c.2911_2912del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001083606.3:c.2911_2912del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001083607.3:c.2911_2912del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354918.2:c.3208_3209del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_149061.2:n.4103_4104del - 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
SCV000549047	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 26, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16419085, 16301862, 29498494, 29575684, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000549047

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 26, 2022)

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

PTCH mutations: distribution and analyses.

Lindström E, Shimokawa T, Toftgård R, Zaphiropoulos PG.

Hum Mutat. 2006 Mar;27(3):215-9. Review.

PubMed [citation]

PMID:: 16419085

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000549047.5

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 409150). This sequence change creates a premature translational stop signal (p.Met1122Valfs*22) in the PTCH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTCH1 are known to be pathogenic (PMID: 16301862, 16419085). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with basal cell nevus syndrome, also known as Gorlin syndrome (PMID: 16301862, 29498494, 29575684).

#	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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