Submissions for variant NM_001844.5(COL2A1):c.2862C>T (p.Gly954=)

dbSNP: rs367806541

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269946	SCV001450321	pathogenic	not provided	2017-10-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001269946	SCV001574302	pathogenic	not provided	2023-11-25	criteria provided, single submitter	clinical testing	This sequence change affects codon 954 of the COL2A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL2A1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of Stickler syndrome (PMID: 20179744, 20513134). ClinVar contains an entry for this variant (Variation ID: 988535). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20179744, 20513134). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001269946	SCV001811906	pathogenic	not provided	2024-03-03	criteria provided, single submitter	clinical testing	Non-canonical splice site variant demonstrated to result in loss-of-function (PMID: 20513134); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31781920, 20179744, 34680973, 34169787, 27193475, 26443184, 20513134, 33726816)
Institute of Human Genetics, University of Leipzig Medical Center	RCV002294450	SCV002587077	likely pathogenic	Stickler syndrome type 1	2022-09-30	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PS3, PS4_MOD, PM2_SUP, PP3, PP4
CeGaT Center for Human Genetics Tuebingen	RCV001269946	SCV004033201	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	COL2A1: PVS1, PS4:Moderate, PM2:Supporting, PP1, PS3:Supporting
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV002294450	SCV004045906	pathogenic	Stickler syndrome type 1	2022-12-09	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001269946	SCV005414075	pathogenic	not provided	2024-02-15	criteria provided, single submitter	clinical testing	PP4, PM2, PS3, PS4
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001269946	SCV001808400	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001269946	SCV001956980	pathogenic	not provided		no assertion criteria provided	clinical testing