ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.1048C>G (p.Leu350Val)

gnomAD frequency: 0.00001  dbSNP: rs768046010
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001059236 SCV001223856 uncertain significance Li-Fraumeni syndrome 2023-09-30 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 350 of the TP53 protein (p.Leu350Val). This variant is present in population databases (rs768046010, gnomAD 0.007%). 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: 854234). 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. 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 RCV002402425 SCV002709742 likely benign Hereditary cancer-predisposing syndrome 2021-09-27 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.
Baylor Genetics RCV003462579 SCV004206239 uncertain significance Adrenocortical carcinoma, hereditary 2023-09-03 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV002402425 SCV004359972 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-25 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 350 of the TP53 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have shown that this variant was functional in yeast trancriptional activation studies and human cell growth suppression assays (PMID: 12826609, 30224644). To our knowledge, this variant has not been reported in individuals affected with TP53-related disorders in the literature. This variant has been identified in 1/251008 chromosomes 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.

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