Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000177457 | SCV000322314 | likely pathogenic | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | Functional studies suggest that c.1962 C>T creates a cryptic splice donor site that results in a 35 bp deletion and translational frameshift when/if used, however, in vivo effect of this variant on splicing was not assessed (PMID: 17437277); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30245029, 20513134, 18276201, 17437277) |
| Labcorp Genetics |
RCV000177457 | SCV002221113 | pathogenic | not provided | 2024-12-23 | criteria provided, single submitter | clinical testing | This sequence change affects codon 654 of the COL2A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL2A1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with autosomal dominant Stickler syndrome (PMID: 17437277). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 196618). Studies have shown that this variant is associated with inconclusive levels of altered splicing (PMID: 17437277). For these reasons, this variant has been classified as Pathogenic. |
| Eurofins Ntd Llc |
RCV000177457 | SCV000229316 | uncertain significance | not provided | 2015-01-05 | flagged submission | clinical testing | |
| Prevention |
RCV004734793 | SCV005356801 | likely pathogenic | COL2A1-related disorder | 2024-08-27 | no assertion criteria provided | clinical testing | The COL2A1 c.1962C>T variant is not predicted to result in an amino acid change (p.=). This variant has been reported in a family with Stickler syndrome and functional studies indicated that this variant affected mRNA splicing and resulted in a premature protein termination (Richards et al. 2007. PubMed ID: 17437277) and found in another patient with deafness (reported as NM_033150:c.1755C>T in Table S3, Azaiez et al. 2018. PubMed ID: 30245029). At PreventionGenetics, we have observed this variant in other patients with a COL2A1-relation condition (internal data). This variant is reported in 0.0032% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as likely pathogenic. |