ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.582+6T>C

dbSNP: rs397509375
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000018760 SCV004292657 pathogenic Ehlers-Danlos syndrome, type 4 2024-01-17 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the COL3A1 gene. It does not directly change the encoded amino acid sequence of the COL3A1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Ehlers-Danlos syndrome (PMID: 8320698). This variant is also known as IVS7 T+6 to C+6,. ClinVar contains an entry for this variant (Variation ID: 17220). 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 6, but is expected to preserve the integrity of the reading-frame (PMID: 8320698). This variant disrupts the triple helix domain of COL3A1. 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). In COL3A1, variants that affect these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000018760 SCV000039043 pathogenic Ehlers-Danlos syndrome, type 4 1993-05-01 no assertion criteria provided literature only

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