Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001478081 | SCV001682338 | likely benign | Cowden syndrome 6 | 2020-09-16 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV001478081 | SCV002769002 | uncertain significance | Cowden syndrome 6 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous splice site variant was identified, NM_005163.2(AKT1):c.288-4G>T in intron 4 of the AKT1 gene. This substitution may cause aberrant splicing of exon 5 in the AKT1 gene, and affect protein function; further testing via RNA studies is required to confirm if splicing is altered. However, in silico software does not predict the splice site variant to cause aberrant splicing (NetGene2, NNSPLICE, Human Splicing Finder). The nucleotide at this position has low conservation (PhyloP, UCSC). The variant is present in the gnomAD database at a frequency of 0.0004 (1 heterozygote, 0 homozygotes). It has not been previously observed in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE. |