ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.6205C>T (rs121912855)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414882 SCV000492870 pathogenic Short stature; Failure to thrive; Abnormality of the dentition; Microcephaly; Abnormality of dental enamel; Hyperpigmentation of the skin; Alopecia of scalp; Distal muscle weakness; EMG abnormality; Decreased body weight; Scarring alopecia of scalp; Abnormal blistering of the skin; Nail dystrophy; Scarring 2015-05-07 criteria provided, single submitter clinical testing
GeneDx RCV000498291 SCV000589318 pathogenic not provided 2018-08-07 criteria provided, single submitter clinical testing The R2069C variant in the COL7A1 gene has been reported previously in the homozygous state or with another COL7A1 variant in multiple individuals with dystrophic epidermolysis bullosa (DEB) (Kahofer et al. 2003, Kern et al. 2006, van den Akker et al. 2009, Jerabkova et al. 2013, Danescu et al. 2015). The R2069C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The R2069C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret R2069C as a pathogenic variant.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626608 SCV000747309 pathogenic Abnormal blistering of the skin 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV000498291 SCV000958934 pathogenic not provided 2020-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 2069 of the COL7A1 protein (p.Arg2069Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121912855, ExAC 0.003%). This variant has been observed in individual(s) with dystrophic epidermolysis bullosa (PMID: 12787275, 28830826, 22266148). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17463). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Not Available; Align-GVGD: Class C2). For these reasons, this variant has been classified as Pathogenic. 5
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001199071 SCV001370066 pathogenic Epidermolysis bullosa pruriginosa 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PM3,PP1-M,PP4.
Centogene AG - the Rare Disease Company RCV001251179 SCV001426534 pathogenic Generalized dominant dystrophic epidermolysis bullosa criteria provided, single submitter clinical testing
Biomedical Innovation Departament, CIEMAT RCV001352770 SCV001547352 pathogenic Dystrophic epidermolysis bullosa 2016-01-07 criteria provided, single submitter research
OMIM RCV000019015 SCV000039302 pathogenic Epidermolysis bullosa dystrophica inversa, autosomal recessive 2003-05-01 no assertion criteria provided literature only
Natera, Inc. RCV000019015 SCV001454259 pathogenic Epidermolysis bullosa dystrophica inversa, autosomal recessive 2020-09-16 no assertion criteria provided clinical testing

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