Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002648193 | SCV003523409 | pathogenic | not provided | 2022-08-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with COL11A1-related conditions (PMID: 23026214, 27124789). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn398Metfs*19) in the COL11A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL11A1 are known to be pathogenic (PMID: 20513134, 21035103, 23922384, 25240749, 32427345, 32756486). |
| Mayo Clinic Laboratories, |
RCV002648193 | SCV004225698 | pathogenic | not provided | 2022-10-19 | criteria provided, single submitter | clinical testing | PM2, PM3_strong, PVS1 |
| Center for Genomic Medicine, |
RCV003989809 | SCV004806042 | pathogenic | Stickler syndrome type 2 | 2024-03-25 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV003989809 | SCV005399628 | pathogenic | Stickler syndrome type 2 | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with COL11A1-related skeletal dysplasias and autosomal dominant deafness 37 (MIM#618533). Dominant negative is also a suggested mechanism (OMIM). (I) 0108 - This gene is associated with both recessive and dominant disease. Both missense variants and those predicted to result in a truncated protein have been associated with autosomal recessive and dominant disease. Additionally, autosomal recessive Stickler syndrome is usually caused by variants affecting exon 9 (PMID: 32578940, PMID: 25073711). (I) 0115 - Variants in this gene causing Stickler syndrome are known to have variable expressivity (PMID: 27081569). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0219 - This variant is non-coding in an alternative transcript. However, this variant is coding in the ClinVar predominant transcript, with multiple other pathogenic variants also found within this exon. A publication has suggested that variants with premature termination codons in exon 9, consequently result in milder disease, as they are non-coding in the cartilage-specific isoform (UCSC, PMID: 23922384). (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported many times as pathogenic (DECIPHER), with several within this exon reported in individuals with nonsyndromic hearing loss (PMID: 35885918, PMID: 32371413, ClinVar). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic and likely pathogenic (ClinVar, LOVD), and has been observed in a compound heterozygous and homozygous individual with cleft palate and hearing loss (PMID: 23026214, PMID: 23922384). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |