ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.1007dup (p.Tyr336Ter)

dbSNP: rs2132283619
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001975097 SCV002240926 pathogenic PTEN hamartoma tumor syndrome 2022-10-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PTEN protein in which other variant(s) (p.Tyr379*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1458931). This premature translational stop signal has been observed in individual(s) with clinical features of Cowden syndrome (PMID: 9467011, 20712882, 28086757, 29273943, 29752200, 31336731). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr336*) in the PTEN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acid(s) of the PTEN protein.
MGZ Medical Genetics Center RCV002290822 SCV002581086 pathogenic Macrocephaly-autism syndrome 2022-07-21 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003453884 SCV004189668 pathogenic Cowden syndrome 1 2023-10-09 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987945 SCV004803982 pathogenic Cowden syndrome 2024-01-30 criteria provided, single submitter clinical testing Variant summary: PTEN c.1007dupA (p.Tyr336X) results in a premature termination codon in the pentultimate exon of the PTEN gene, predicted to cause a truncation of the encoded protein. However, nonsense mediated decay is not expected to occur. The variant was absent in 250932 control chromosomes. c.1007dupA or another variant resulting in p.Tyr336X has been reported in the literature in multiple individuals affected with PTEN hamartoma tumor syndrome (e.g. Bubien_2013, Plamper_2018) or affected with Cowden Syndrome or clinical features of Cowden syndrome (e.g. Marsh_1998, Banneau_2010, Pena-Couso_2022). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 20712882, 23335809, 30978501, 9467011, 26612463, 35227301, 29273943). ClinVar contains an entry for this variant (Variation ID: 1458931). Based on the evidence outlined above, the variant was classified as pathogenic.

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