NM_000094.4(COL7A1):c.6205C>T (p.Arg2069Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 18, 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:: RCV000498291.11

Allele description [Variation Report for NM_000094.4(COL7A1):c.6205C>T (p.Arg2069Cys)]

NM_000094.4(COL7A1):c.6205C>T (p.Arg2069Cys)

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.6205C>T (p.Arg2069Cys)

HGVS:

NC_000003.12:g.48575218G>A
NG_007065.1:g.25035C>T
NM_000094.4:c.6205C>TMANE SELECT
NP_000085.1:p.Arg2069Cys
NP_000085.1:p.Arg2069Cys
LRG_286t1:c.6205C>T
LRG_286:g.25035C>T
LRG_286p1:p.Arg2069Cys
NC_000003.11:g.48612651G>A
NM_000094.3:c.6205C>T
Q02388:p.Arg2069Cys

Protein change:

R2069C; ARG2069CYS

Links:

UniProtKB: Q02388#VAR_064996; OMIM: 120120.0041; dbSNP: rs121912855

NCBI 1000 Genomes Browser:

rs121912855

Molecular consequence:

NM_000094.4:c.6205C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000589318	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 27, 2022)	germline	clinical testing	Citation Link,
SCV000958934	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 18, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12787275, 22266148, 28830826, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000589318

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 27, 2022)

germline

clinical testing

Citation Link,

SCV000958934

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 18, 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

Dystrophic epidermolysis bullosa inversa with COL7A1 mutations and absence of GDA-J/F3 protein.

Kahofer P, Bruckner-Tuderman L, Metze D, Lemmink H, Scheffer H, Smolle J.

Pediatr Dermatol. 2003 May-Jun;20(3):243-8.

PubMed [citation]

PMID:: 12787275

Novel and recurrent COL7A1 mutation in a Polish population.

Wertheim-Tysarowska K, Sobczyńska-Tomaszewska A, Kowalewski C, Kutkowska-Kaźmierczak A, Woźniak K, Niepokój K, Klausegger A, Sypniewska-Jutkiewicz J, Stępień A, Bal J.

Eur J Dermatol. 2012 Jan-Feb;22(1):23-8. doi: 10.1684/ejd.2011.1583.

PubMed [citation]

PMID:: 22266148

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000589318.5

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

Description

Reported as heterozygous in two affected individuals without another COL7A1 variant; however, studies were not comprehensive and did not exclude other variants/molecular causes (Hamidi et al., 2016; Danescu et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18558993, 32860008, 31589614, 32484238, 16484981, 20598510, 25201089, 26707537, 28830826, 27746867, 31001817, 34286919, 34308104, 34674926, 22266148, 34826142, 19665875, 12787275)

#	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, SCV000958934.5

#	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 replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2069 of the COL7A1 protein (p.Arg2069Cys). This variant is present in population databases (rs121912855, gnomAD 0.004%). This missense change has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 12787275, 22266148, 28830826). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17463). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL7A1 protein function with a negative predictive value of 95%. 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: Apr 15, 2024

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