Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000084537 | SCV000614050 | pathogenic | not provided | 2017-04-04 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000626752 | SCV000747455 | pathogenic | Dementia | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000626753 | SCV000747456 | pathogenic | Frontotemporal dementia; Memory impairment; Mental deterioration | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000687510 | SCV000815082 | pathogenic | Frontotemporal dementia | 2020-02-01 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 9 of the MAPT gene. It does not directly change the encoded amino acid sequence of the MAPT protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with frontotemporal dementia in many families (PMID: 9641683, 28097206, 19786698, 11912108, 20045477, 11708988, 17923640, 11971081, 19766248) and likely represents a founder mutation originating from Northern Wales (PMID:19365643). This variant is also known as IVS10+16C>T or 10+16C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 98222). Experimental studies have shown that this intronic change disrupts the stem-loop structure thus leading to aberrant splicing and increased incorporation of exon 10 of MAPT mRNA (PMID: 9641683, 10329720, 26136155, 19914360). Mouse models recapitulate the human frontotemporal dementia phenotype (PMID:23680655). For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV000687510 | SCV001150160 | pathogenic | Frontotemporal dementia | 2018-01-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000084537 | SCV001767383 | pathogenic | not provided | 2021-08-30 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that this variant leads to aberrant splicing of exon 10 (Umeda et al., 2013; Hutton et al., 1998); Not observed at significant frequency in large population cohorts (Lek et al., 2016); Nearby splice variants reported in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 19365643, 27905268, 23885714, 10443890, 7783864, 8940276, 23680655, 19914360, 26136155, 27082848, 28097206, 29253099, 29930232, 11402146, 27594586, 25683866, 20045477, 19786698, 18525295, 14755449, 11708988, 11641718, 10446810, 10202939, 9392579, 9088499, 7936288, 11255441, 31031559, 31537715, 9641683, 19884572, 12847166, 15372253, 17923640, 19766248, 11971081, 11971082, 11912108) |
OMIM | RCV000687510 | SCV000035578 | pathogenic | Frontotemporal dementia | 2009-10-01 | no assertion criteria provided | literature only | |
VIB Department of Molecular Genetics, |
RCV000084537 | SCV000116673 | not provided | not provided | no assertion provided | not provided |