Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000459820 | SCV000545265 | uncertain significance | Li-Fraumeni syndrome | 2024-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 44 of the TP53 protein (p.Met44Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 406565). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function with a negative predictive value of 97.5%. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609). 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 | RCV001011072 | SCV001171351 | likely benign | Hereditary cancer-predisposing syndrome | 2020-10-28 | 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. |
Genome- |
RCV001011072 | SCV002582153 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002289589 | SCV002582716 | uncertain significance | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing |