ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.5820G>A (rs200972872)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497540 SCV000589317 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing The c.5820 G>A variant in the COL7A1 gene has been reported previously with another COL7A1 variant in association with recessive dystrophic epidermolysis bullosa (RDEB) (Teracina et al., 1998, Gardella et al. 2002). This variant reduces the quality of the splice donor site in intron 70, and is expected to cause abnormal gene splicing and exon skipping of exon 70, resulting in an internally deleted protein (Terracina et al. 1998). The c.5820 G>A variant is observed in 23/126,384 (0.018%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). We interpret c.5820 G>A as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000763114 SCV000893656 likely pathogenic Recessive dystrophic epidermolysis bullosa; Pretibial epidermolysis bullosa; Dominant dystrophic epidermolysis bullosa with absence of skin; Transient bullous dermolysis of the newborn; Epidermolysis bullosa pruriginosa; Nail disorder, nonsyndromic congenital, 8; Generalized dominant dystrophic epidermolysis bullosa 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000497540 SCV000934821 pathogenic not provided 2020-10-19 criteria provided, single submitter clinical testing This sequence change affects codon 1940 of the COL7A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL7A1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs200972872, ExAC 0.02%). This variant has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 9804332, 31001817, 31930626). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 431810). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with skipping of exon 70, but is expected to preserve the integrity of the reading-frame (PMID: 9804332). 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.
Illumina Clinical Services Laboratory,Illumina RCV001148931 SCV001309852 uncertain significance Dystrophic epidermolysis bullosa 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Biomedical Innovation Departament, CIEMAT RCV001148931 SCV001547333 pathogenic Dystrophic epidermolysis bullosa 2018-11-26 criteria provided, single submitter research
Natera, Inc. RCV001272350 SCV001454262 pathogenic Epidermolysis bullosa dystrophica inversa, autosomal recessive 2020-09-16 no assertion criteria provided clinical testing

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