Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001980143 | SCV002237324 | uncertain significance | not provided | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 885 of the COL11A1 protein (p.Thr885Met). This variant is present in population databases (rs550201657, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL11A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1448483). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV003355702 | SCV004070772 | uncertain significance | Inborn genetic diseases | 2023-06-16 | criteria provided, single submitter | clinical testing | The c.2654C>T (p.T885M) alteration is located in exon 33 (coding exon 33) of the COL11A1 gene. This alteration results from a C to T substitution at nucleotide position 2654, causing the threonine (T) at amino acid position 885 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV004785408 | SCV005399929 | uncertain significance | Fibrochondrogenesis 1 | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.2, this variant is classified as 3A-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with COL11A1-related skeletal dysplasia. (I) 0108 - This gene is associated with both recessive and dominant disease, however inheritance is usually dominant for Stickler and Marshall syndromes (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from threonine to methionine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (10 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (3 heterozygotes, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated collagen triple helix repeat region (NCBI, PDB). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (VCGS # 20G001699 and 20G001700). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Autoinflammatory diseases unit, |
RCV004770307 | SCV005381977 | likely pathogenic | Marshall syndrome | 2024-08-21 | no assertion criteria provided | clinical testing |