ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.634+2T>C

dbSNP: rs727504114
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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, Clingen RCV001172260 SCV001335267 pathogenic PTEN hamartoma tumor syndrome 2020-03-23 reviewed by expert panel curation PTEN c.634+2T>C (IVS6+2T>C) 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). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5' to c.1121 (NM_000314.4). PM2: Absent in large sequenced populations PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 28677221)
Ambry Genetics RCV002356807 SCV002654801 pathogenic Hereditary cancer-predisposing syndrome 2021-03-09 criteria provided, single submitter clinical testing The c.634+2T>C intronic pathogenic mutation results from a T to C substitution two nucleotides after coding exon 6 in the PTEN gene. This mutation has been identified in an individual with Cowden syndrome (CS) (Chen HJ et al. Hum Mutat, 2017 10;38:1372-1377). RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data; Chen HJ et al. Hum Mutat, 2017 10;38:1372-1377). Another alteration impacting the same donor site (c.634+5G>A) has been shown to have a similar impact on splicing in an individual with PTEN hamartoma tumor syndrome (PTHS) (Boccone L et al. Am. J. Med. Genet. A, 2008 Jan;146A:257-60; Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Cancer Genomic Medicine Translational Research Lab, Cleveland Clinic Genomic Medicine Institute RCV000516099 SCV000579236 pathogenic Cowden syndrome 1 2017-05-26 no assertion criteria provided research

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