Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489508 | SCV000577410 | uncertain significance | not provided | 2025-02-23 | criteria provided, single submitter | clinical testing | Damages or destroys the splice donor site in intron 34, and is expected to cause abnormal gene splicing; if the splice outcome is exon skip, the loss of the encoded residues in the triple helical region is expected to disrupt normal protein folding and function (PMID: 25240749); Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 22189268, 20513134, 25240749) |
| Labcorp Genetics |
RCV000489508 | SCV002272693 | pathogenic | not provided | 2024-11-11 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 35 of the COL11A1 gene. It does not directly change the encoded amino acid sequence of the COL11A1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of autosomal dominant Stickler syndrome (PMID: 20513134; internal data). It has also been observed to segregate with disease in related individuals. This variant is also known as c.2755+5G>A. ClinVar contains an entry for this variant (Variation ID: 374386). 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. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000414977 | SCV000328741 | likely pathogenic | Stickler syndrome type 2 | 2016-05-01 | no assertion criteria provided | clinical testing | Our laboratory reported two molecular diagnoses in COL11A1 (NM_080630.2:c.2754+5G>A) and KRIT1 (NM_194456.1:c.146_147del) in an individual with hearing loss, tics, dysmorphic features, macrocephaly, vision loss, chronic otitis media, reactive airway disease, food allergy, urticaria, eczema, and keratosis pilaris. |
| Autoinflammatory diseases unit, |
RCV000414977 | SCV005381980 | pathogenic | Stickler syndrome type 2 | 2024-09-25 | no assertion criteria provided | clinical testing |