VCV001706597.2 - ClinVar

NM_000494.4(COL17A1):c.3686dup (p.Val1231fs)

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.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000494.4(COL17A1):c.3686dup (p.Val1231fs)

Variation ID: 1706597 Accession: VCV001706597.2

Type and length

Duplication, 1 bp

Location

Cytogenetic: 10q25.1 10: 104034700-104034701 (GRCh38) [ NCBI UCSC ] 10: 105794458-105794459 (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	Oct 1, 2022	Feb 14, 2024	Sep 4, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000494.4:c.3686dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000485.3:p.Val1231fs	frameshift
NC_000010.11:g.104034705dup
NC_000010.10:g.105794463dup
NG_007069.1:g.56180dup
LRG_1249:g.56180dup
LRG_1249t1:c.3686dup	LRG_1249p1:p.Val1231fs

... more HGVS ... less HGVS

Protein change

V1231fs

Other names

Canonical SPDI

NC_000010.11:104034700:GGGGG:GGGGGG

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.
COL17A1		-	-	GRCh38 GRCh37	1414	1484

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.
Epidermolysis bullosa, junctional 4, intermediate	Pathogenic (1)	criteria provided, single submitter	Sep 16, 2022	RCV002285206.2
not provided	Pathogenic (1)	criteria provided, single submitter	Sep 4, 2023	RCV003565513.2

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.
Pathogenic (Sep 16, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Epidermolysis bullosa, junctional 4, intermediate (X-linked inheritance) Affected status: yes Allele origin: germline	Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin Additional submitter: CUBI - Core Unit Bioinformatics, Berlin Institute of Health Accession: SCV002574956.1 First in ClinVar: Oct 01, 2022 Last updated: Oct 01, 2022	Sex: male Tissue: Blood
Pathogenic (Sep 04, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004320883.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Publications: PubMed (5) PubMed: 16473856‚ 17344927‚ 20301304‚ 21357940‚ 24319098 Comment: This sequence change creates a premature translational stop signal (p.Val1231Cysfs11) in the COL17A1 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Val1231Cysfs11) in the COL17A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL17A1 are known to be pathogenic (PMID: 16473856, 17344927, 20301304, 21357940, 24319098). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL17A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1706597). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Val1231Cysfs*11) in the COL17A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL17A1 are known to be pathogenic (PMID: 16473856, 17344927, 20301304, 21357940, 24319098). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL17A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1706597). For these reasons, this variant has been classified as Pathogenic.

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

Title	Author	Journal	Year	Link
Junctional Epidermolysis Bullosa.	Adam MP	-	2018	PMID: 20301304
A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta.	Poulter JA	Human molecular genetics	2014	PMID: 24319098
Molecular mechanisms of phenotypic variability in junctional epidermolysis bullosa.	Kiritsi D	Journal of medical genetics	2011	PMID: 21357940
Retrospective diagnosis of fatal BP180-deficient non-Herlitz junctional epidermolysis bullosa suggested by immunofluorescence (IF) antigen-mapping of parental carriers bearing enamel defects.	Murrell DF	The Journal of investigative dermatology	2007	PMID: 17344927
Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants.	Varki R	Journal of medical genetics	2006	PMID: 16473856

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000494.4(COL17A1):c.3686dup (p.Val1231fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...