ClinVar Miner

Submissions for variant NM_001377265.1(MAPT):c.889C>A (p.Arg297Ser) (rs150983093)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000791003 SCV000930266 uncertain significance Frontotemporal dementia 2019-04-27 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000791004 SCV000930267 uncertain significance Pick disease 2019-04-27 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000791005 SCV000930268 uncertain significance Multiple system atrophy 2019-04-27 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000791006 SCV000930269 uncertain significance Progressive supranuclear ophthalmoplegia 2019-04-27 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354954 SCV001549688 uncertain significance not provided no assertion criteria provided clinical testing The MAPT p.R222S variant was identified in the literature in a patient with early onset frontotemporal lobar degeneration who also had two PPT1 variants (Jeung_2015_PMID:29595823). The variant was identified in dbSNP (ID: rs150983093) and ClinVar (classified as uncertain significance by Genomic Research Center, Shahid Beheshti University of Medical Sciences). The variant was identified in control databases in 80 of 274120 chromosomes at a frequency of 0.0002918 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 22 of 24108 chromosomes (freq: 0.000913), Other in 5 of 7046 chromosomes (freq: 0.00071), Latino in 24 of 35096 chromosomes (freq: 0.000684) and European (non-Finnish) in 29 of 123262 chromosomes (freq: 0.000235), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.R222 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001354954 SCV001740683 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001354954 SCV001970859 likely benign not provided no assertion criteria provided clinical testing

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