ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.293T>G (p.Leu98Arg) (rs781647403)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467489 SCV000541585 uncertain significance PTEN hamartoma tumor syndrome 2016-04-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 98 of the PTEN protein (p.Leu98Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature, but has been observed in an individual with a PTEN-related disease in the Invitae database. This missense change is located within a functionally conserved phosphatase domain of the PTEN protein and a high percentage of previously reported PTEN missense mutations have been found within this domain (PMID: 17167516, 18794875). These observations suggest that a missense substitution within this domain may affect protein function. In addition, algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. However, these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is located within an important functional domain of PTEN, but its impact on protein function is uncertain. While it is absent from the population and observed in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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