Submissions for variant NM_000314.7(PTEN):c.889G>T (p.Asp297Tyr) (rs370064195)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483528	SCV000565451	uncertain significance	not provided	2015-08-31	criteria provided, single submitter	clinical testing	This variant is denoted PTEN c.889G>T at the cDNA level, p.Asp297Tyr (D297Y) at the protein level, and results in the change of an Aspartic Acid to a Tyrosine (GAT>TAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PTEN Asp297Tyr was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Aspartic Acid and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PTEN Asp297Tyr occurs at a position that is conserved across mammals and is located in the C2 domain (Nguyen 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether PTEN Asp297Tyr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae	RCV000538140	SCV000645630	uncertain significance	PTEN hamartoma tumor syndrome	2018-09-11	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with tyrosine at codon 297 of the PTEN protein (p.Asp297Tyr). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PTEN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000570235	SCV000663576	uncertain significance	Hereditary cancer-predisposing syndrome	2017-12-01	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient evidence

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