Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001140400 | SCV001300653 | uncertain significance | Fleck corneal dystrophy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Neuberg Centre For Genomic Medicine, |
RCV001140400 | SCV005382412 | uncertain significance | Fleck corneal dystrophy | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense c.308G>A (p.Arg103His) variant in PIKFYVE gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg103His variant is present with allele frequency of 0.0004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. Multiple lines of computational evidence (Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid of p.Arg103His in PIKFYVE is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 103 is changed to a His changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). |