Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foundation for Research in Genetics and Endocrinology, |
RCV000850226 | SCV000965587 | uncertain significance | Alzheimer disease 3; Frontotemporal dementia | 2019-06-27 | criteria provided, single submitter | clinical testing | A heterozygous variant c.517_519delTTG (p.Leu174del) in Exon-6 has been observed in the PSEN1 gene. The proband, born of a non-consanguineous marriage, presented with clinical indication of progressive memory loss and behavioral changes. Her MRI of brain showed diffuse cerebral and cerebellar atrophy, frontal and temporal lobe atrophy. Her multiple family members have similar symptoms. The patient in our clinical analysis was observed with the said variant in an autosomal dominant mode of inheritance. The variant has not been reported in the 1000 genomes and ExAC databases. The in-silico predictions of the variant are probably damaging by MutationTaster2. In summary, the said variant meets our criteria to be classified as uncertain significance based on the mode of inheritance, in silico prediction, allele frequency in population databases and lack of segregation study. |