Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000492906 | SCV000582515 | uncertain significance | not provided | 2017-05-12 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TMEM5 gene. The c.914+6 T>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.914+6 T>G variant not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.914+6 T>G reduces the natural splice donor site and may and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000492906 | SCV001511899 | likely pathogenic | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 5 of the RXYLT1 gene. It does not directly change the encoded amino acid sequence of the RXYLT1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs748809209, gnomAD 0.002%). This variant has been observed in individual(s) with clinical features of congenital muscular dystrophy (PMID: 30017359). ClinVar contains an entry for this variant (Variation ID: 429848). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 5, but is expected to preserve the integrity of the reading-frame (PMID: 30017359). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Department Of Genetics, |
RCV000698558 | SCV002574733 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 | 2022-06-30 | criteria provided, single submitter | clinical testing |