Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000757597 | SCV000885890 | uncertain significance | not provided | 2017-06-02 | criteria provided, single submitter | clinical testing | The p.Ile481Thr variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Exome Aggregation Consortium (ExAC) browser. The isoleucine at position 481 is weakly conserved (considering 12 species, Alamut v.2.9.0) but computational analyses of the effects of the p.Ile481Thr variant on protein structure and function predict a deleterious effect (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Ile481Thr variant with certainty |
Labcorp Genetics |
RCV000757597 | SCV002998930 | uncertain significance | not provided | 2022-08-09 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 618776). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 481 of the PCDH15 protein (p.Ile481Thr). 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. |
Natera, |
RCV001835950 | SCV002091074 | uncertain significance | Usher syndrome type 1F | 2021-02-23 | no assertion criteria provided | clinical testing |