ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.563A>G (p.Tyr188Cys)

dbSNP: rs2132269501
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237464 SCV002009264 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003509691 SCV004295309 uncertain significance PTEN hamartoma tumor syndrome 2023-11-11 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 188 of the PTEN protein (p.Tyr188Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PTEN-related conditions (PMID: 27876779). ClinVar contains an entry for this variant (Variation ID: 1319460). 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 PTEN protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects PTEN function (PMID: 29785012). 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.
GeneDx RCV003237464 SCV005921368 pathogenic not provided 2024-10-17 criteria provided, single submitter clinical testing Published functional studies demonstrate decreased protein abundance and wild type-like phosphatase activity (PMID: 29785012, 29706350); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported as a germline variant in a child with myelodysplastic syndrome (PMID: 27876779); This variant is associated with the following publications: (PMID: 29785012, 29706350, 18626510, 27876779)

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