ClinVar Miner

Submissions for variant NM_001377265.1(MAPT):c.14G>A (p.Arg5His) (rs63750959)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services,Illumina RCV000266864 SCV000403475 likely benign MAPT-Related Spectrum Disorders 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV000015330 SCV001412838 uncertain significance Frontotemporal dementia 2019-09-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 5 of the MAPT protein (p.Arg5His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs63750959, ExAC 0.07%). This variant has been observed in several individuals with MAPT-related conditions (PMID: 11921059, 22312439, 26200045, 26601740, 28462717, 28923025); however, this variant has also been identified in reportedly unaffected individuals (PMID: 22312439, 25604855) and has been predicted to have very low penetrance if it is associated with disease (PMID: 30279455). ClinVar contains an entry for this variant (Variation ID: 14261). This variant has been reported to affect MAPT protein function (PMID: 11921059). This variant disrupts the p.Arg5 amino acid residue in MAPT. Other variant(s) that disrupt this residue have been observed in individuals with MAPT-related conditions (PMID: 12325083, 18803694, 23043292), which suggests that this may be a clinically significant amino acid residue. 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.
OMIM RCV000015330 SCV000035589 pathogenic Frontotemporal dementia 2002-04-01 no assertion criteria provided literature only

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