Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000213709 | SCV000271806 | uncertain significance | not specified | 2016-03-03 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Glu419Lys var iant in MITF has been previously identified by our laboratory in one individual with Waardenburg syndrome who also had a dominant pathogenic variant in another gene known to cause Waardenburg syndrome. This variant has been identified in 0. 21% (140/66732) of European chromosomes by the Exome Aggregation Consortium (ExA C, http://exac.broadinstitute.org; dbSNP rs149617956). Although this variant has been seen in the general population, its frequency is not high enough to rule o ut a pathogenic role. Computational prediction tools and conservation analysis d o not provide strong support for or against an impact to the protein. In summary , while the clinical significance of the p.Glu419Lys variant is uncertain, its f requency in the general population suggests that it is more likely to be benign. |
| Invitae | RCV001853454 | SCV002120318 | uncertain significance | not provided | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 4290 of the ADGRV1 protein (p.Arg4290His). This variant is present in population databases (rs762515714, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 228709). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. |
| Ambry Genetics | RCV002519631 | SCV003528038 | uncertain significance | Inborn genetic diseases | 2022-10-03 | criteria provided, single submitter | clinical testing | The c.12869G>A (p.R4290H) alteration is located in exon 64 (coding exon 64) of the ADGRV1 gene. This alteration results from a G to A substitution at nucleotide position 12869, causing the arginine (R) at amino acid position 4290 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |