ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.492G>A (p.Lys164=) (rs146629065)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478062 SCV000571312 uncertain significance not provided 2016-08-19 criteria provided, single submitter clinical testing This variant is denoted PTEN c.492G>A at the DNA level. This variant is silent at the coding level, preserving a Lysine at codon 164. This variant is not predicted to cause abnormal splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. PTEN c.492G>A was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. The nucleotide which is altered, a guanine (G) at base 492, is conserved across species. Based on currently available information, it is unclear whether PTEN c.492G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565708 SCV000671719 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000645052 SCV000766792 uncertain significance PTEN hamartoma tumor syndrome 2019-03-08 criteria provided, single submitter clinical testing This sequence change affects codon 164 of the PTEN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PTEN protein. This variant also falls at the last nucleotide of exon 5 of the PTEN coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs146629065, ExAC 0.04%). This variant has not been reported in the literature in individuals with PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 421963). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.
Color RCV000565708 SCV001354511 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-04 criteria provided, single submitter clinical testing

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