Submissions for variant NM_000314.8(PTEN):c.71A>G (p.Asp24Gly)

dbSNP: rs797044910

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000190739	SCV000244180	pathogenic	Hereditary cancer-predisposing syndrome	2017-06-01	criteria provided, single submitter	clinical testing	The p.D24G pathogenic mutation (also known as c.71A>G), located in coding exon 1 of the PTEN gene, results from an A to G substitution at nucleotide position 71. The aspartic acid at codon 24 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in three individuals meeting relaxed International Cowden Consortium operational criteria for Cowden syndrome and was identified as a de novo mutation in an individual with a clinical diagnosis of Cowden syndrome in our internal cohort (Tan MH et al. Am. J. Hum. Genet. 2011 Jan; 88(1):42-56). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000234212	SCV000284600	pathogenic	PTEN hamartoma tumor syndrome	2020-10-11	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with glycine at codon 24 of the PTEN protein (p.Asp24Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Cowden or Cowden-like syndrome (PMID: 21194675, 22503188, 24498881). ClinVar contains an entry for this variant (Variation ID: 208723). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare missense variant that is absent in the general population and has been reported in several affected individuals. For these reasons, it has been classified as Pathogenic.
Mendelics	RCV000234212	SCV001138122	likely pathogenic	PTEN hamartoma tumor syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268658	SCV001447744	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003454489	SCV004188731	likely pathogenic	Cowden syndrome 1	2023-09-25	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 21194675, 22503188, 24901346, 10232405, 23335809]. Functional studies indicate this variant impacts protein function [PMID: 17213812].
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000234212	SCV000898144	pathogenic	PTEN hamartoma tumor syndrome	2018-11-23	no assertion criteria provided	clinical testing