ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.5532+5G>A

gnomAD frequency: 0.00001  dbSNP: rs1210912397
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001975025 SCV002242011 pathogenic not provided 2024-09-17 criteria provided, single submitter clinical testing This sequence change falls in intron 64 of the COL7A1 gene. It does not directly 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 (no rsID available, gnomAD 0.01%). This variant has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 21182502, 32484238). 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: 1458606). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 64, but is expected to preserve the integrity of the reading-frame (PMID: 21182502). 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.
GeneDx RCV001975025 SCV003925938 pathogenic not provided 2023-04-10 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss of function (Huang et al., 2011) in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 21182502, 25525159, 32484238)
Fulgent Genetics, Fulgent Genetics RCV005032019 SCV005664191 pathogenic Recessive dystrophic epidermolysis bullosa; Pretibial dystrophic epidermolysis bullosa; Dominant dystrophic epidermolysis bullosa with absence of skin; Transient bullous dermolysis of the newborn; Epidermolysis bullosa pruriginosa; Nonsyndromic congenital nail disorder 8; Generalized dominant dystrophic epidermolysis bullosa 2024-05-09 criteria provided, single submitter clinical testing

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