Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413977 | SCV000491421 | likely pathogenic | not provided | 2016-02-09 | criteria provided, single submitter | clinical testing | The R131H variant in the KCNK9 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R131H variant was not observed 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 R131H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The R131H variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
| Baylor Genetics | RCV000679851 | SCV000807197 | likely pathogenic | Birk-Barel syndrome | criteria provided, single submitter | clinical testing | ||
| Ambry Genetics | RCV001266147 | SCV001444319 | likely pathogenic | Inborn genetic diseases | 2018-12-07 | criteria provided, single submitter | clinical testing | |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000413977 | SCV001468105 | likely pathogenic | not provided | 2020-10-22 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000679851 | SCV002034859 | likely pathogenic | Birk-Barel syndrome | 2021-08-17 | criteria provided, single submitter | clinical testing | The KCNK9 c.392G>A (p.Arg131His) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. However, multiple clinical laboratories in ClinVar have provided a likely pathogenic classification for this variant, which was noted to have occurred de novo in a male patient who was tested by the Baylor Genetics laboratory, and whose information was presumably published (Yang et al. 2014). This variant is not found in version 2.1.1 or version 3.1.1 of the Genome Aggregation Database despite its location in a region of good sequence coverage, which suggests the variant is rare. Multiple lines of computational evidence suggest that this variant will have a deleterious impact on the protein. This variant was identified in a de novo state. Based on the available evidence, the p.Arg131His variant is classified as likely pathogenic for KCNK9-imprinting syndrome, also known as Birk-Barel syndrome. |
| Department of Genetics, |
RCV000679851 | SCV002102961 | likely pathogenic | Birk-Barel syndrome | 2021-07-01 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000679851 | SCV003841024 | pathogenic | Birk-Barel syndrome | 2023-01-25 | no assertion criteria provided | literature only |