ClinVar Miner

Submissions for variant NM_002087.4(GRN):c.99C>A (p.Asp33Glu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001124955 SCV001283975 uncertain significance Grn-related frontotemporal lobar degeneration with Tdp43 inclusions 2017-09-14 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001242925 SCV001416047 uncertain significance Grn-related frontotemporal lobar degeneration with Tdp43 inclusions; Ceroid lipofuscinosis, neuronal, 11 2019-11-11 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 33 of the GRN protein (p.Asp33Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs63750742, ExAC 0.03%). This variant has been observed in individual(s) affected with frontotemporal dementia, Alzheimer disease and Parkinson's disease. (PMID: 27632209, 26811050, 18565828, 18838661, 26811050). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.

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