NM_000094.4(COL7A1):c.5720_5721delinsAT (p.Gly1907Asp) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 2, 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:: RCV000413574.9

Allele description [Variation Report for NM_000094.4(COL7A1):c.5720_5721delinsAT (p.Gly1907Asp)]

NM_000094.4(COL7A1):c.5720_5721delinsAT (p.Gly1907Asp)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000094.4(COL7A1):c.5720_5721delinsAT (p.Gly1907Asp)

HGVS:

NC_000003.12:g.48576537_48576538delinsAT
NG_007065.1:g.23715_23716delinsAT
NM_000094.4:c.5720_5721delinsATMANE SELECT
NP_000085.1:p.Gly1907Asp
NP_000085.1:p.Gly1907Asp
LRG_286t1:c.5720_5721delinsAT
LRG_286:g.23715_23716delinsAT
LRG_286p1:p.Gly1907Asp
NC_000003.11:g.48613970_48613971delinsAT
NM_000094.3:c.5720_5721delGAinsAT
NM_000094.3:c.5720_5721delinsAT

Protein change:

G1907D

Links:

dbSNP: rs1057517725

NCBI 1000 Genomes Browser:

rs1057517725

Molecular consequence:

NM_000094.4:c.5720_5721delinsAT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Rattus norvegicus protein kinase, interferon inducible double stranded RNA dependent activator, mRNA (cDNA clone MGC:114506 IMAGE:7456528), complete cds
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490495	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 26, 2022)	germline	clinical testing	Citation Link,
SCV001415520	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 2, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16971478, 20555349, 21448560, 7695699, 8218237, 19344236, 22058051, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490495

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 26, 2022)

germline

clinical testing

Citation Link,

SCV001415520

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 2, 2023)

germline

clinical testing

PubMed (8)
[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

Inversa dystrophic epidermolysis bullosa is caused by missense mutations at specific positions of the collagenic domain of collagen type VII.

Chiaverini C, Charlesworth AV, Youssef M, Cuny JF, Rabia SH, Lacour JP, Meneguzzi G.

J Invest Dermatol. 2010 Oct;130(10):2508-11. doi: 10.1038/jid.2010.159. Epub 2010 Jun 17. No abstract available.

PubMed [citation]

PMID:: 20555349

See all PubMed Citations (8)

Details of each submission

From GeneDx, SCV000490495.3

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

Description

Located in the highly conserved Gly-X-Y repeat of the collagenous domain; Glycine substitution variants in this region of the COLVII protein destabilize the collagen triple helix resulting in skin fragility due to poor anchoring of the basement membrane to the underlying dermis (Pfendner and Lucky, 2018); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21448560, 16971478, 20555349)

#	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, SCV001415520.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1907 of the COL7A1 protein (p.Gly1907Asp). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with recessive dystrophic epidermolysis bullosa (PMID: 16971478, 20555349, 21448560). 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: 372342). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the triple helix domain of COL7A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236), and variants at these glycine residues in COL7A1 are more frequently observed in individuals with disease than in the general population (PMID: 22058051). However, the clinical significance of this observation remains uncertain since only a limited number of affected individuals have been described to date. 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: Sep 29, 2024

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