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NM_000264.4(PTCH1):c.1526G>A (p.Gly509Asp) AND Gorlin syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 2, 2016
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:
RCV000477105.1

Allele description

NM_000264.4(PTCH1):c.1526G>A (p.Gly509Asp)

Gene:
PTCH1:patched 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.32
Genomic location:
Preferred name:
NM_000264.4(PTCH1):c.1526G>A (p.Gly509Asp)
HGVS:
  • NC_000009.12:g.95476835C>T
  • NG_007664.1:g.45131G>A
  • NM_000264.4:c.1526G>A
  • NM_001083602.2:c.1328G>A
  • NP_000255.2:p.Gly509Asp
  • NP_001077071.1:p.Gly443Asp
  • LRG_515t1:c.1526G>A
  • LRG_515t2:c.1328G>A
  • LRG_515:g.45131G>A
  • LRG_515p1:p.Gly509Asp
  • LRG_515p2:p.Gly443Asp
  • NC_000009.11:g.98239117C>T
  • NM_000264.3:c.1526G>A
Protein change:
G443D
Links:
dbSNP: rs1060502268
NCBI 1000 Genomes Browser:
rs1060502268
Molecular consequence:
  • NM_000264.4:c.1526G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Gorlin syndrome (BCNS)
Synonyms:
Basal cell nevus syndrome
Identifiers:
MedGen: C0004779; Orphanet: 377; OMIM: 109400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000549037Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 2, 2016) 		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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000549037.2

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

Description

This sequence change replaces glycine with aspartic acid at codon 509 of the PTCH1 protein (p.Gly509Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (PMID: 12655573, 24204797, 16301862, 16088933). In one of these individuals, this variant has been shown to arise de novo (PMID: 16088933). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that has been described in several affected individuals, including one individual in which this variant arose de novo. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jul 21, 2018