Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000192926 | SCV000246402 | uncertain significance | not specified | 2014-12-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000766979 | SCV000533189 | uncertain significance | not provided | 2017-07-13 | criteria provided, single submitter | clinical testing | The P2490L variant in the ANK3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P2490L variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P2490L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret P2490L as a variant of uncertain significance. |
| Fulgent Genetics, |
RCV000763663 | SCV000894543 | uncertain significance | Intellectual disability-hypotonia-spasticity-sleep disorder syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000766979 | SCV001043902 | likely benign | not provided | 2023-12-02 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003927757 | SCV004738363 | uncertain significance | ANK3-related condition | 2024-02-12 | criteria provided, single submitter | clinical testing | The ANK3 c.7469C>T variant is predicted to result in the amino acid substitution p.Pro2490Leu. This variant was reported in a compound heterozygous state in an individual with a neurodevelopmental disorder (Yang et al 2019. PubMed ID: 31451636). Functional studies revealed that this variant interferes with a conformational change that is required for ANK3 to bind with another neuronal protein (Yang et al 2019. PubMed ID: 31451636). This variant is reported in 0.23% of alleles in individuals of Latino descent in gnomAD, which is at a higher frequency than expected for disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |