ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.1212A>T (p.Ter404Cys) (rs876660879)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000645070 SCV001244244 pathogenic PTEN hamartoma tumor syndrome 2019-11-22 reviewed by expert panel curation PTEN c.1212A>T (p.Ter404CysextTer8) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor ClinVar Organization ID: 26957) PM2: Absent in large sequenced populations (PMID 27535533). PM4: Variant causes protein extension. PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributors ClinVar Organization ID: 26957, SCV000278659.5)
Ambry Genetics RCV000214783 SCV000278659 likely pathogenic Hereditary cancer-predisposing syndrome 2016-08-25 criteria provided, single submitter clinical testing Well-characterized mutation at same position;Structural Evidence;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000645070 SCV000766812 uncertain significance PTEN hamartoma tumor syndrome 2017-11-20 criteria provided, single submitter clinical testing This sequence change disrupts the translational stop signal of the PTEN mRNA. It is expected to extend the length of the PTEN protein by 8 additional amino acid residues. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 234144). A different variant in affecting this stop codon (p.*404Serext*8) has been reported in an individual with macrocephaly, enlarged periventricular spaces and pervasive developmental disorder (PMID: 24375884). This suggests that stop loss variants may impact PTEN protein function. 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.

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