NM_000094.4(COL7A1):c.3840del (p.Gly1281fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 6, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000413788.14

Allele description [Variation Report for NM_000094.4(COL7A1):c.3840del (p.Gly1281fs)]

NM_000094.4(COL7A1):c.3840del (p.Gly1281fs)

Gene:

COL7A1:collagen type VII alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000094.4(COL7A1):c.3840del (p.Gly1281fs)

HGVS:

NC_000003.12:g.48585612del
NG_007065.1:g.14642del
NM_000094.4:c.3840delMANE SELECT
NP_000085.1:p.Gly1281fs
NP_000085.1:p.Gly1281fs
LRG_286t1:c.3840del
LRG_286:g.14642del
LRG_286p1:p.Gly1281fs
NC_000003.11:g.48623044del
NC_000003.11:g.48623045del
NM_000094.3:c.3840del
NM_000094.3:c.3840delC

Protein change:

G1281fs

Links:

dbSNP: rs757688782

NCBI 1000 Genomes Browser:

rs757688782

Molecular consequence:

NM_000094.4:c.3840del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490484	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 26, 2022)	germline	clinical testing	Citation Link,
SCV000956457	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 6, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10504458, 16971478, 23786535, 24317394, 28492532
SCV002019682	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 14, 2021)	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

SCV000490484

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 26, 2022)

germline

clinical testing

Citation Link,

SCV000956457

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 6, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002019682

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 14, 2021)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comparative mutation detection screening of the type VII collagen gene (COL7A1) using the protein truncation test, fluorescent chemical cleavage of mismatch, and conformation sensitive gel electrophoresis.

Whittock NV, Ashton GH, Mohammedi R, Mellerio JE, Mathew CG, Abbs SJ, Eady RA, McGrath JA.

J Invest Dermatol. 1999 Oct;113(4):673-86.

PubMed [citation]

PMID:: 10504458

Epidermolysis bullosa. II. Type VII collagen mutations and phenotype-genotype correlations in the dystrophic subtypes.

Varki R, Sadowski S, Uitto J, Pfendner E.

J Med Genet. 2007 Mar;44(3):181-92. Epub 2006 Sep 13.

PubMed [citation]

PMID:: 16971478
PMCID:: PMC2598021

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000490484.4

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28168442, 24317394, 20301481, 29500833, 29625052, 26689913, 34426522, 23786535, 16971478, 10504458)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV000956457.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gly1281Valfs*44) in the COL7A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). This variant is present in population databases (rs757688782, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with epidermolysis bullosa dystrophica (PMID: 10504458, 16971478, 23786535, 24317394). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 372332). For these reasons, this variant has been classified as Pathogenic.

#	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

From Revvity Omics, Revvity, SCV002019682.3

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

#	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: Mar 16, 2024

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