Submissions for variant NM_001854.4(COL11A1):c.3816+1G>C

dbSNP: rs398122828

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University of Leipzig Medical Center	RCV001253407	SCV001429097	pathogenic	Marshall syndrome	2018-03-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001579902	SCV002584414	pathogenic	not provided	2023-02-14	criteria provided, single submitter	clinical testing	Identified in multiple unrelated patients with Marshall syndrome in the published literature (Annunen et al., 1999; Khalifa et al., 2014); Damages or destroys the splice donor site in intron 50, and is expected to cause abnormal gene splicing; if the splice outcome is exon skip, the loss of the encoded residues in the triple helical region is expected to disrupt normal protein folding and function (Stenson et al., 2014; Acke et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); Also known as IVS50+1G>C; This variant is associated with the following publications: (PMID: 25525159, 25073711, 10486316, 25240749)
Invitae	RCV001579902	SCV003523344	pathogenic	not provided	2023-04-29	criteria provided, single submitter	clinical testing	Studies have shown that disruption of this splice site results in skipping of exon 51, but is expected to preserve the integrity of the reading-frame (PMID: 9529347). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 976188). Disruption of this splice site has been observed in individual(s) with autosomal dominant Marshall or Stickler syndrome (PMID: 9529347, 19449424, 25240749). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 50 of the COL11A1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579902	SCV001808939	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001579902	SCV001955934	pathogenic	not provided		no assertion criteria provided	clinical testing