VCV002503342.2 - ClinVar

NM_000264.5(PTCH1):c.3945del (p.Tyr1316fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000264.5(PTCH1):c.3945del (p.Tyr1316fs)

Variation ID: 2503342 Accession: VCV002503342.2

Type and length

Deletion, 1 bp

Location

Cytogenetic: 9q22.32 9: 95447311 (GRCh38) [ NCBI UCSC ] 9: 98209593 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 4, 2023	Nov 20, 2023	Nov 25, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000264.5:c.3945del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000255.2:p.Tyr1316fs	frameshift
NM_001083603.3:c.3942del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001077072.1:p.Tyr1315fs	frameshift
NM_000264.3:c.3940delC	NP_000255.2:p.Tyr1316Thrfs	frameshift
NM_001083602.3:c.3747del	NP_001077071.1:p.Tyr1250fs	frameshift
NM_001083604.3:c.3492del	NP_001077073.1:p.Tyr1165fs	frameshift
NM_001083605.3:c.3492del	NP_001077074.1:p.Tyr1165fs	frameshift
NM_001083606.3:c.3492del	NP_001077075.1:p.Tyr1165fs	frameshift
NM_001083607.3:c.3492del	NP_001077076.1:p.Tyr1165fs	frameshift
NM_001354918.2:c.3789del	NP_001341847.1:p.Tyr1264fs	frameshift
NR_149061.2:n.4684del		non-coding transcript variant
NC_000009.12:g.95447316del
NC_000009.11:g.98209598del
NG_007664.1:g.74655del
LRG_515:g.74655del
LRG_515t1:c.3945del
LRG_515t2:c.3742del	LRG_515p2:p.Tyr1250Thrfs

... more HGVS ... less HGVS

Protein change

Y1165fs, Y1250fs, Y1264fs, Y1315fs, Y1316fs

Other names

Canonical SPDI

NC_000009.12:95447310:GGGGGG:GGGGG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PTCH1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4024	5237

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Uncertain significance (1)	criteria provided, single submitter	Nov 25, 2022	RCV003230176.1
Turner syndrome	Pathogenic (1)	criteria provided, single submitter	Jan 1, 2021	RCV003389563.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Nov 25, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV003927665.1 First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023	Comment: Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation as the last 132 amino acids are … (more) Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation as the last 132 amino acids are replaced with 55 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously reported as pathogenic or benign in association with neurodevelopmental disorders to our knowledge; De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; This variant is associated with the following publications: (PMID: 33082750) (less)
Pathogenic (Jan 01, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Turner syndrome Turner's syndrome and colonoma (Autosomal dominant inheritance) Affected status: yes Allele origin: unknown	DBGen Ocular Genomics Accession: SCV004101714.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: Class 5 ACMG Guidelines, 2015 (PMID:25741868) Sex: female Geographic origin: Mexico Tissue: DNA

Comment:

Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation as the last 132 amino acids are replaced with 55 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously reported as pathogenic or benign in association with neurodevelopmental disorders to our knowledge; De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; This variant is associated with the following publications: (PMID: 33082750)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Nov 25, 2023

ClinVar Genomic variation as it relates to human health

NM_000264.5(PTCH1):c.3945del (p.Tyr1316fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...