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NM_000094.4(COL7A1):c.6527dup (p.Gly2177fs) AND COL7A1-related disorder

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 16, 2024
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:
RCV003972555.3

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)

Name:
COL7A1-related disorder
Synonyms:
COL7A1-related condition; COL7A1- related disorders
Identifiers:

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004788168PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Aug 31, 2024) 		germlineclinical testing

SCV004813109Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Feb 16, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families.

Cuadrado-Corrales N, Sánchez-Jimeno C, García M, Escámez MJ, Illera N, Hernández-Martín A, Trujillo-Tiebas MJ, Ayuso C, Del Rio M.

BMC Med Genet. 2010 Sep 29;11:139. doi: 10.1186/1471-2350-11-139.

PubMed [citation]
PMID:
20920254
PMCID:
PMC2957067

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004788168.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The COL7A1 c.6527dupC variant is predicted to result in a frameshift and premature protein termination (p.Gly2177Trpfs*113). This variant has been reported in the homozygous or compound heterozygous state in multiple unrelated individuals with epidermolysis bullosa dystrophica (see for example - referred to as 6527insC in Hovnanian et al. 1997. PubMed ID: 9326325; Cuadrado-Corrales et al. 2010. PubMed ID: 20920254; Almaani et al. 2011. PubMed ID: 21448560). This variant is reported in 0.043% of alleles in individuals of Latino descent in gnomAD. Frameshift variants in COL7A1 are expected to be pathogenic. This variant is interpreted as pathogenic.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004813109.1

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

Description

Variant summary: COL7A1 c.6527dupC (p.Gly2177TrpfsX113) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 6.8e-05 in 250676 control chromosomes. c.6527dupC has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Dystrophic Epidermolysis Bullosa, Recessive with the variant described as a founder mutation of Spanish origin (e.g. Cuadrado-Corrales_2010). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 20920254). ClinVar contains an entry for this variant (Variation ID: 372345). Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 24, 2024