NM_000264.5(PTCH1):c.3406G>A (p.Gly1136Arg) AND Gorlin syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 10, 2023
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:: RCV001241702.8

Allele description [Variation Report for NM_000264.5(PTCH1):c.3406G>A (p.Gly1136Arg)]

NM_000264.5(PTCH1):c.3406G>A (p.Gly1136Arg)

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.3406G>A (p.Gly1136Arg)

HGVS:

NC_000009.12:g.95453521C>T
NG_007664.1:g.68445G>A
NM_000264.5:c.3406G>AMANE SELECT
NM_001083602.3:c.3208G>A
NM_001083603.3:c.3403G>A
NM_001083604.3:c.2953G>A
NM_001083605.3:c.2953G>A
NM_001083606.3:c.2953G>A
NM_001083607.3:c.2953G>A
NM_001354918.2:c.3250G>A
NP_000255.2:p.Gly1136Arg
NP_001077071.1:p.Gly1070Arg
NP_001077072.1:p.Gly1135Arg
NP_001077073.1:p.Gly985Arg
NP_001077074.1:p.Gly985Arg
NP_001077075.1:p.Gly985Arg
NP_001077076.1:p.Gly985Arg
NP_001341847.1:p.Gly1084Arg
LRG_515t1:c.3406G>A
LRG_515:g.68445G>A
NC_000009.11:g.98215803C>T
NM_000264.3:c.3406G>A
NR_149061.2:n.4145G>A

Protein change:

G1070R

Links:

dbSNP: rs1838655420

NCBI 1000 Genomes Browser:

rs1838655420

Molecular consequence:

NM_000264.5:c.3406G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083602.3:c.3208G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083603.3:c.3403G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083604.3:c.2953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083605.3:c.2953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083606.3:c.2953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083607.3:c.2953G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354918.2:c.3250G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_149061.2:n.4145G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001414739	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32741058, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001414739

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2023)

germline

clinical testing

PubMed (2)
[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

Novel PTCH1 mutation in Gorlin-Goltz syndrome potentially altered interactions with lipid bilayer.

Gao Q, Xu N, Yang C, Yang K, Bian Z.

Oral Dis. 2021 Apr;27(3):475-483. doi: 10.1111/odi.13586. Epub 2020 Aug 31. No abstract available.

PubMed [citation]

PMID:: 32741058

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001414739.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

ClinVar contains an entry for this variant (Variation ID: 966913). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PTCH1 protein function. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individuals with clinical features of basal cell nevus syndrome (Gorlin syndrome) (PMID: 32741058; Invitae; external communication). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1136 of the PTCH1 protein (p.Gly1136Arg). This variant is not present in population databases (gnomAD no frequency).

#	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

ClinVar

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