Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010231 | SCV001170394 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-27 | criteria provided, single submitter | clinical testing | The p.H397Y variant (also known as c.1189C>T), located in coding exon 9 of the PTEN gene, results from a C to T substitution at nucleotide position 1189. The histidine at codon 397 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002479203 | SCV002790197 | uncertain significance | Macrocephaly-autism syndrome; Familial meningioma; Malignant tumor of prostate; Glioma susceptibility 2; Cowden syndrome 1 | 2021-11-25 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001010231 | SCV004357080 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-14 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with tyrosine at codon 397 of the PTEN protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV003619734 | SCV004512923 | uncertain significance | PTEN hamartoma tumor syndrome | 2023-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 397 of the PTEN protein (p.His397Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. ClinVar contains an entry for this variant (Variation ID: 818542). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |