Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489508 | SCV000577410 | pathogenic | not provided | 2017-03-30 | criteria provided, single submitter | clinical testing | The c.2754+5G>A variant in the COL11A1 gene, using alternate nomenclature c.2755+5G>A, has been reported previously in the heterozygous state in association with Stickler syndrome (Richards et al., 2010). This variant destroys the splice donor site at intron 35, and is expected to cause abnormal gene splicing. The c.2754+5G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.2754+5G>A as a pathogenic variant. |
Labcorp Genetics |
RCV000489508 | SCV002272693 | pathogenic | not provided | 2023-10-23 | 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; Invitae). 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. |