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NM_000264.5(PTCH1):c.589T>C (p.Trp197Arg) AND Gorlin syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 28, 2017
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:
RCV000534590.7

Allele description [Variation Report for NM_000264.5(PTCH1):c.589T>C (p.Trp197Arg)]

NM_000264.5(PTCH1):c.589T>C (p.Trp197Arg)

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.589T>C (p.Trp197Arg)
HGVS:
  • NC_000009.12:g.95482199A>G
  • NG_007664.1:g.39767T>C
  • NM_000264.5:c.589T>CMANE SELECT
  • NM_001083602.3:c.391T>C
  • NM_001083603.3:c.586T>C
  • NM_001083604.3:c.136T>C
  • NM_001083605.3:c.136T>C
  • NM_001083606.3:c.136T>C
  • NM_001083607.3:c.136T>C
  • NM_001354918.2:c.589T>C
  • NM_001354919.2:c.391T>C
  • NP_000255.2:p.Trp197Arg
  • NP_001077071.1:p.Trp131Arg
  • NP_001077072.1:p.Trp196Arg
  • NP_001077073.1:p.Trp46Arg
  • NP_001077074.1:p.Trp46Arg
  • NP_001077075.1:p.Trp46Arg
  • NP_001077076.1:p.Trp46Arg
  • NP_001341847.1:p.Trp197Arg
  • NP_001341848.1:p.Trp131Arg
  • LRG_515t1:c.589T>C
  • LRG_515:g.39767T>C
  • NC_000009.11:g.98244481A>G
  • NM_000264.3:c.589T>C
  • NR_149061.2:n.1494T>C
Protein change:
W131R
Links:
dbSNP: rs1312950307
NCBI 1000 Genomes Browser:
rs1312950307
Molecular consequence:
  • NM_000264.5:c.589T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083602.3:c.391T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083603.3:c.586T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083604.3:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083605.3:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083606.3:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001083607.3:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354918.2:c.589T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354919.2:c.391T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149061.2:n.1494T>C - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000623051Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Feb 28, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV000623051.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces tryptophan with arginine at codon 197 of the PTCH1 protein (p.Trp197Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PTCH1-related disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024