Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000528860 | SCV000655136 | uncertain significance | Tumor predisposition syndrome 3 | 2023-11-16 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 42 of the POT1 protein (p.Asp42Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 475035). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | RCV002448787 | SCV002682087 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-18 | criteria provided, single submitter | clinical testing | The p.D42E variant (also known as c.126T>G), located in coding exon 3 of the POT1 gene, results from a T to G substitution at nucleotide position 126. The aspartic acid at codon 42 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with POT1-related disease and was shown to segregate with disease in at least one family (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |