Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000633335 | SCV000754557 | uncertain significance | Li-Fraumeni syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 30224644). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 528241). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 355 of the TP53 protein (p.Ala355Val). |
Ambry Genetics | RCV001009801 | SCV001169915 | likely benign | Hereditary cancer-predisposing syndrome | 2021-07-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Color Diagnostics, |
RCV001009801 | SCV001344585 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-03 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002289921 | SCV002582722 | uncertain significance | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001009801 | SCV002583214 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV004568384 | SCV005054351 | uncertain significance | Adrenocortical carcinoma, hereditary | 2023-11-29 | criteria provided, single submitter | clinical testing |