Total submissions: 11
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 | 2023-09-24 | 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 (gnomAD no frequency). This variant has been observed in individual(s) with frontotemporal dementia (PMID: 9641683, 11708988, 11912108, 11971081, 17923640, 19365643, 19766248, 19786698, 20045477, 28097206). It is commonly reported in individuals of Welsh ancestry (PMID: 19365643). This variant is also known as IVS10+16C>T or 10+16C>T. ClinVar contains an entry for this variant (Variation ID: 98222). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects MAPT function (PMID: 9641683, 10329720, 19914360, 23680655, 26136155). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. For these reasons, this variant has been classified as Pathogenic. |
Institute Of Human Genetics Munich, |
RCV000687510 | SCV001150160 | pathogenic | Frontotemporal dementia | 2018-01-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000084537 | SCV001767383 | pathogenic | not provided | 2023-01-12 | 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 (gnomAD); This variant is associated with the following publications: (PMID: 19365643, 27905268, 23885714, 10443890, 7783864, 8940276, 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, 31810826, 32804255, 31914217, 34099697, 10329720, 23680655, 34561610, 34158384) |
Molecular Genetics, |
RCV000687510 | SCV002498672 | pathogenic | Frontotemporal dementia | 2022-04-05 | criteria provided, single submitter | clinical testing | This sequence change in MAPT is an intronic variant located in intron 10. This variant is absent from gnomAD v2.1 and v3.1. This variant is a common Welsh founder mutation and the most common variant in frontotemporal dementia (FTD) cases with British descent (PMID: 19365643). The variant has been reported to segregate with FTD in multiple families (PMID: 9641683). The results from multiple in silico splicing predictors (SpliceAI, MaxEntScan, NNSplice) indicate that this variant may not impact splicing of MAPT. However, RT-PCR and mini-gene assays demonstrated that the variant increases exon 10 RNA expression expected to result in a change in the ratio of tau isoforms of three amino-acid repeats to those of four amino-acid repeats (PMID: 9641683). A transgenic mouse model of the variant also recapitulates the human phenotype and demonstrates much higher levels of four-repeat tau and the adult stage (PMID: 23680655). Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as PATHOGENIC. Following criteria are met: PS3, PS4, PP1_Strong, PM2_Supporting, BP4. |
Preventiongenetics, |
RCV003415858 | SCV004118409 | pathogenic | MAPT-related condition | 2022-09-16 | criteria provided, single submitter | clinical testing | The MAPT c.1920+16C>T variant is predicted to interfere with splicing. This variant has been reported to be causative for frontotemporal dementia and results in altered splicing based on functional studies (Hutton et al. 1998. PubMed ID: 9641683; Umeda et al. 2013. PubMed ID: 23680655; Wang et al. 2010. PubMed ID: 19914360; Heutink. 2000. PubMed ID: 10767321; Sposito et al. 2015. PubMed ID: 26136155). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is consistently classified as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/98222/). This variant is interpreted as pathogenic. |
Mayo Clinic Laboratories, |
RCV000084537 | SCV004224201 | pathogenic | not provided | 2023-06-16 | criteria provided, single submitter | clinical testing | BP4, BP7, PM2 |
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 |