NM_000264.5(PTCH1):c.3358G>A (p.Glu1120Lys) AND Gorlin syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV001211332.7

Allele description [Variation Report for NM_000264.5(PTCH1):c.3358G>A (p.Glu1120Lys)]

NM_000264.5(PTCH1):c.3358G>A (p.Glu1120Lys)

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.3358G>A (p.Glu1120Lys)

HGVS:

NC_000009.12:g.95453569C>T
NG_007664.1:g.68397G>A
NM_000264.5:c.3358G>AMANE SELECT
NM_001083602.3:c.3160G>A
NM_001083603.3:c.3355G>A
NM_001083604.3:c.2905G>A
NM_001083605.3:c.2905G>A
NM_001083606.3:c.2905G>A
NM_001083607.3:c.2905G>A
NM_001354918.2:c.3202G>A
NP_000255.2:p.Glu1120Lys
NP_001077071.1:p.Glu1054Lys
NP_001077072.1:p.Glu1119Lys
NP_001077073.1:p.Glu969Lys
NP_001077074.1:p.Glu969Lys
NP_001077075.1:p.Glu969Lys
NP_001077076.1:p.Glu969Lys
NP_001341847.1:p.Glu1068Lys
LRG_515t1:c.3358G>A
LRG_515:g.68397G>A
NC_000009.11:g.98215851C>T
NM_000264.3:c.3358G>A
NR_149061.2:n.4097G>A

Protein change:

E1054K

Links:

dbSNP: rs1838662287

NCBI 1000 Genomes Browser:

rs1838662287

Molecular consequence:

NM_000264.5:c.3358G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083602.3:c.3160G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083603.3:c.3355G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083604.3:c.2905G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083605.3:c.2905G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083606.3:c.2905G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001083607.3:c.2905G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354918.2:c.3202G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_149061.2:n.4097G>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
SCV001382868	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001382868

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001382868.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt PTCH1 protein function. ClinVar contains an entry for this variant (Variation ID: 941537). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1120 of the PTCH1 protein (p.Glu1120Lys).

#	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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