Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001026929 | SCV001189404 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-22 | criteria provided, single submitter | clinical testing | The c.78C>G variant (also known as p.T26T), located in coding exon 1, results from a C to G substitution at nucleotide position 78 of the PTEN gene, the penultimate nucleotide of exon 1. This nucleotide substitution does not change the amino acid at codon 26. This alteration has been reported in an individual with colorectal cancer diagnosed at age 44 (Pearlman R et al. JAMA Oncol 2017 Apr;3(4):464-471). This alteration was observed with an allele frequency of 0.00014 in 7,051 unselected female breast cancer patients and was not observed in 11,241 female controls of Japanese ancestry (Momozowa Y et al. Nat Commun 2018 10;9(1):4083). This nucleotide position is well conserved in available vertebrate species. This alteration is located adjacent to a predicted U12-type intron for which available in silico tools are not reliable as determined by the ClinGen PTEN variant curation expert panel (Mester JL et al. Hum Mutat. 2018 11;39:1581-1592). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001862389 | SCV002266364 | uncertain significance | PTEN hamartoma tumor syndrome | 2022-11-04 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 827320). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with PTEN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 26 of the PTEN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PTEN protein. It affects a nucleotide within the consensus splice site. |