Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001884489 | SCV002156590 | uncertain significance | not provided | 2023-04-15 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of OTUD6B-related intellectual disability with dysmorphic facies, seizures, and distal limb anomalies (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 310 of the OTUD6B protein (p.Ser310Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. ClinVar contains an entry for this variant (Variation ID: 1388293). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Center of Genomic medicine, |
RCV003388618 | SCV004100327 | likely pathogenic | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies | 2023-08-01 | criteria provided, single submitter | clinical testing | This variant is present in compound heterozygosity with another variant in the same gene. These two variants were identified in two brothers with similar phenotype (global development delay, autistic features and epilepsy/seizures) |
| Prevention |
RCV003416542 | SCV004109150 | uncertain significance | OTUD6B-related disorder | 2022-10-17 | criteria provided, single submitter | clinical testing | The OTUD6B c.929C>T variant is predicted to result in the amino acid substitution p.Ser310Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0036% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-92097053-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Gene |
RCV001884489 | SCV005378538 | uncertain significance | not provided | 2023-11-30 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |