Submissions for variant NM_001844.5(COL2A1):c.3106C>T (p.Arg1036Ter)

dbSNP: rs748459670

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000479858	SCV000230653	pathogenic	not provided	2015-09-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000479858	SCV000568530	pathogenic	not provided	2023-06-23	criteria provided, single submitter	clinical testing	Has been reported in multiple individuals with Stickler syndrome (Richards et al., 2006; Hoornaert et al., 2010; Richards et al., 2010; Savasta et al., 2015; Barat-Houari et al., 2016a; Kondo et al., 2016; Huang et al., 2020; Choi et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25809783, 25525159, 16752401, 20179744, 23891399, 29453956, 26443184, 27408751, 29661559, 20513134, 34680973, 32756486)
Mendelics	RCV000988819	SCV001138704	pathogenic	Stickler syndrome type 1	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV000479858	SCV001581178	pathogenic	not provided	2023-11-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1036*) in the COL2A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). This variant is present in population databases (rs748459670, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Stickler syndrome type 1 (PMID: 16752401, 25809783). ClinVar contains an entry for this variant (Variation ID: 197503). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000479858	SCV004564461	pathogenic	not provided	2023-02-27	criteria provided, single submitter	clinical testing	The COL2A1 c.3106C>T; p.Arg1036Ter variant (rs748459670) is reported in the literature in individuals with Stickler syndrome (Choi 2021, Richards 2006, Savasta 2015). This variant is also reported in ClinVar (Variation ID: 197503). It is only found on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Choi SI et al. Genetic Characteristics and Phenotype of Korean Patients with Stickler Syndrome: A Korean Multicenter Analysis Report No. 1. Genes (Basel). 2021 Oct 5;12(10):1578. PMID: 34680973. Richards AJ et al. High efficiency of mutation detection in type 1 stickler syndrome using a two-stage approach: vitreoretinal assessment coupled with exon sequencing for screening COL2A1. Hum Mutat. 2006 Jul;27(7):696-704. PMID: 16752401. Savasta S et al. Stickler syndrome associated with epilepsy: report of three cases. Eur J Pediatr. 2015 May;174(5):697-701. PMID: 25809783.