ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.278A>G (p.His93Arg) (rs121909238)

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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 RCV000645075 SCV000886857 pathogenic PTEN hamartoma tumor syndrome 2018-11-28 reviewed by expert panel curation PTEN c.278A>G (p.His93Arg) 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(s) ClinVar Organization ID: 26957) PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. PM2: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PS3_P: Abnormal in vitro cellular assay or transgenic model with phenotype different from wild type that does not meet PS3. (PMID 26579216, 25647146, 20718038, 21828076, 29373119, 29785012, 29706350) PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 15805158, internal laboratory contributor(s) ClinVar Organization ID: 26957)
Invitae RCV000645075 SCV000766817 pathogenic PTEN hamartoma tumor syndrome 2019-03-28 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 93 of the PTEN protein (p.His93Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with clinical features of PTEN hamartoma tumor syndrome, including an individual in whom this variant was reported to be de novo (PMID: 24345843, 15805158, 25647146). ClinVar contains an entry for this variant (Variation ID: 7848). This variant has been reported to affect PTEN protein function (PMID: 20718038, 21828076, 25647146, 22505997, 26579216). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.His93 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9685848, 24778394, 21828076, 10866302). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008298 SCV000028505 pathogenic Macrocephaly/autism syndrome 2005-04-01 no assertion criteria provided literature only

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