Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236057 | SCV000294141 | uncertain significance | not provided | 2016-04-12 | criteria provided, single submitter | clinical testing | The R689W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different missense variant at the same position (R689Q) has been reported previously in an individual with hereditary sensory neuropathy (Antoniadi et al., 2015). The R689W variant was not observed in approximately 6,500 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 R689W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Fulgent Genetics, |
RCV002479948 | SCV002781626 | uncertain significance | Medulloblastoma; Familial dysautonomia | 2021-10-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004020940 | SCV004864132 | uncertain significance | not specified | 2023-11-06 | criteria provided, single submitter | clinical testing | The c.2065C>T (p.R689W) alteration is located in exon 19 (coding exon 18) of the IKBKAP gene. This alteration results from a C to T substitution at nucleotide position 2065, causing the arginine (R) at amino acid position 689 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001276230 | SCV001462228 | uncertain significance | Familial dysautonomia | 2020-01-24 | no assertion criteria provided | clinical testing |