NM_000094.4(COL7A1):c.5932C>T (p.Arg1978Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 29, 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:: RCV000523202.5

Allele description [Variation Report for NM_000094.4(COL7A1):c.5932C>T (p.Arg1978Ter)]

NM_000094.4(COL7A1):c.5932C>T (p.Arg1978Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000094.4(COL7A1):c.5932C>T (p.Arg1978Ter)

HGVS:

NC_000003.12:g.48575673G>A
NG_007065.1:g.24580C>T
NM_000094.4:c.5932C>TMANE SELECT
NP_000085.1:p.Arg1978Ter
NP_000085.1:p.Arg1978Ter
LRG_286t1:c.5932C>T
LRG_286:g.24580C>T
LRG_286p1:p.Arg1978Ter
NC_000003.11:g.48613106G>A
NM_000094.3:c.5932C>T
p.Arg1978Term

Protein change:

R1978*

Links:

dbSNP: rs1368134215

NCBI 1000 Genomes Browser:

rs1368134215

Molecular consequence:

NM_000094.4:c.5932C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000617659	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Oct 30, 2017)	germline	clinical testing	Citation Link,
SCV004292729	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16971478, 10504458, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000617659

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Oct 30, 2017)

germline

clinical testing

Citation Link,

SCV004292729

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 29, 2023)

germline

clinical testing

PubMed (3)
[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

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

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000617659.2

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

Description

The R1978X pathogenic variant in the COL7A1 gene has been reported previously in multiple individuals with dystrophic epidermolysis bullosa (Gardella et al., 2000; Sawamura et al., 2005; Natsuga et al., 2010; Rodriguez et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1978X variant is observed in 1/14,974 (0.007%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). We interpret R1978X as a pathogenic variant.

#	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, SCV004292729.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg1978*) 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 (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with COL7A1-related conditions (PMID: 10504458). ClinVar contains an entry for this variant (Variation ID: 449469). 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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