ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.71A>G (p.Asp24Gly) (rs797044910)

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Total submissions: 5
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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.
Invitae 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
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

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