ClinVar Miner

Submissions for variant NM_002087.4(GRN):c.970G>A (p.Ala324Thr) (rs63750541)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000706214 SCV000835253 uncertain significance Grn-related frontotemporal lobar degeneration with Tdp43 inclusions; Ceroid lipofuscinosis, neuronal, 11 2019-09-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 324 of the GRN protein (p.Ala324Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs63750541, ExAC 0.1%). This variant has been observed in individuals affected with frontotemporal dementia (PMID: 18192287, 20142524). ClinVar contains an entry for this variant (Variation ID: 98165). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc RCV000084468 SCV001144921 benign not provided 2019-07-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001128038 SCV001287429 likely benign Grn-related frontotemporal lobar degeneration with Tdp43 inclusions 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
VIB Department of Molecular Genetics, University of Antwerp RCV000084468 SCV000116604 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.