ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.253+1dup

dbSNP: rs876660082
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214537 SCV000277205 pathogenic Hereditary cancer-predisposing syndrome 2017-12-08 criteria provided, single submitter clinical testing The c.253+1dupG intronic pathogenic mutation results from a duplication of the first nucleotide after coding exon 4 of the PTEN gene. Using the BDGP and ESEfinder splice site prediction tools, the strength of the native donor splice site is maintained, but shifted downstream one nucleotide resulting in a translational frameshift with a predicted alternate stop codon; however, direct evidence is unavailable. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000558017 SCV000645560 likely pathogenic PTEN hamartoma tumor syndrome 2017-05-13 criteria provided, single submitter clinical testing In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may shift the splice donor site one nucleotide downstream and out-of-frame, thereby altering normal RNA splicing. However, this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with a PTEN-related disease. ClinVar contains an entry for this variant (Variation ID: 232932). This sequence change affects a donor splice site in intron 4 of the PTEN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
National Institute of Neuroscience, National Center of Neurology and Psychiatry RCV001310253 SCV001438318 pathogenic Macrocephaly-autism syndrome criteria provided, single submitter research

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