ClinVar

Description

Variant summary: Variant summary: COL3A1 c.951+4A>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by published/reported functional studies. The variant was absent in 251244 control chromosomes. c.951+4A>T has been reported in the literature in at-least one individual affected with Ehlers-Danlos Syndrome, Vascular Type (Pepin_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 24922459). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Although one well recognized diagnostic laboratory specializing in the diagnosis of collagen related disorders has submitted a clinical significance assesment as Pathogenic before 2014. This submitter is the institution that identified the single reported case of this variant in an individual with Ehlers-Danlos Syndrome, Vascular Type ascertained above (Pepin_2014). Based on the evidence outlined above, the variant was classified as likely pathogenic.