Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000318990 | SCV000336613 | uncertain significance | not provided | 2015-11-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000686838 | SCV000814375 | uncertain significance | Bethlem myopathy 1A | 2024-05-18 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 40 of the COL6A3 gene. It does not directly change the encoded amino acid sequence of the COL6A3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs190667494, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with COL6A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 284126). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Gene |
RCV000318990 | SCV001819117 | uncertain significance | not provided | 2021-03-17 | criteria provided, single submitter | clinical testing | In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge |
| Revvity Omics, |
RCV000318990 | SCV003833025 | uncertain significance | not provided | 2020-01-30 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV003225058 | SCV003921817 | uncertain significance | Ullrich congenital muscular dystrophy 1A | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene. A dominant negative mechanism has been shown to result from missense variants affecting a glycine residue within a Gly-X-Y triple helical repeat, while loss of function is associated with recessive disease due to other missense and protein-truncating variants (OMIM, PMID: 20301676). (I) 0108 - This gene is associated with both recessive and dominant disease. This gene is associated with autosomal recessive dystonia 27 (MIM#616411) and autosomal recessive and dominant Bethlem myopathy 1 (MIM#158810) and Ullrich congenital muscular dystrophy 1 (MIM#254090). (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (37 heterozygotes, 0 homozygotes). (SP) 0508 - In silico predictions for abnormal splicing are conflicting. (I) 0705 - No comparable non-canonical splice site variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. It has been reported as uncertain significance in ClinVar. (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) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |