NM_000094.4(COL7A1):c.6527dup (p.Gly2177fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 24, 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:: RCV000413123.11

Allele description [Variation Report for NM_000094.4(COL7A1):c.6527dup (p.Gly2177fs)]

NM_000094.4(COL7A1):c.6527dup (p.Gly2177fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000094.4(COL7A1):c.6527dup (p.Gly2177fs)

HGVS:

NC_000003.12:g.48573870dup
NG_007065.1:g.26388dup
NM_000094.4:c.6527dupMANE SELECT
NP_000085.1:p.Gly2177fs
NP_000085.1:p.Gly2177fs
LRG_286t1:c.6527dup
LRG_286:g.26388dup
LRG_286p1:p.Gly2177fs
NC_000003.11:g.48611297_48611298insG
NC_000003.11:g.48611303dup
NM_000094.3:c.6527dup
NM_000094.3:c.6527dup
NM_000094.3:c.6527dupC
NM_000094.4:c.6527dupCMANE SELECT
p.Gly2177Trpfs*113

Protein change:

G2177fs

Links:

dbSNP: rs768128088

NCBI 1000 Genomes Browser:

rs768128088

Molecular consequence:

NM_000094.4:c.6527dup - 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
SCV000490503	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 2, 2021)	germline	clinical testing	Citation Link,
SCV000942042	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 24, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16971478, 9326325, 20920254, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490503

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 2, 2021)

germline

clinical testing

Citation Link,

SCV000942042

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 24, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

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

Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation.

Hovnanian A, Rochat A, Bodemer C, Petit E, Rivers CA, Prost C, Fraitag S, Christiano AM, Uitto J, Lathrop M, Barrandon Y, de Prost Y.

Am J Hum Genet. 1997 Sep;61(3):599-610.

PubMed [citation]

PMID:: 9326325
PMCID:: PMC1715975

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000490503.5

#	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; This variant is associated with the following publications: (PMID: 16971478, 21448560, 31001817, 9326325, 20920254, 23947675, 28973459, 31589614, 29242947, 20184583, 29272047)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000942042.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gly2177Trpfs*113) 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 (rs768128088, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 9326325, 20920254). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It is commonly reported in individuals of Spanish ancestry (PMID: 9326325, 20920254). ClinVar contains an entry for this variant (Variation ID: 372345). 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

Last Updated: Nov 24, 2024

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