Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000227727 | SCV000284592 | uncertain significance | PTEN hamartoma tumor syndrome | 2019-04-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 142 of the PTEN protein (p.Arg142Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature as a germline variant in individuals with PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 237646). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 | RCV000565516 | SCV000666970 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-13 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
Color | RCV000565516 | SCV000912948 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-05 | criteria provided, single submitter | clinical testing | |
Gharavi Laboratory, |
RCV000782196 | SCV000920668 | uncertain significance | not provided | 2018-09-16 | no assertion criteria provided | research |