ClinVar Miner

Submissions for variant NM_018965.4(TREM2):c.197C>T (p.Thr66Met)

gnomAD frequency: 0.00004  dbSNP: rs201258663
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001852102 SCV002240118 pathogenic not provided 2024-08-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 66 of the TREM2 protein (p.Thr66Met). This variant is present in population databases (rs201258663, gnomAD 0.04%). This missense change has been observed in individuals with autosomal dominant Alzheimer disease and/or autosomal recessive frontotemporal dementia (PMID: 23150934, 23318515, 24899047, 29557178). ClinVar contains an entry for this variant (Variation ID: 192242). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects TREM2 function (PMID: 24990881, 25615530, 28559417). For these reasons, this variant has been classified as Pathogenic.
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen RCV004699120 SCV005201049 likely pathogenic Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 criteria provided, single submitter clinical testing The detected variant has a low frequency in gnomAD (0,005390 %) and ist only reported in heterozygous occurence. Bioinformatic predicition is deleterious (CaddPhred, SIFT, MutationTaster). The variant has been reported in literature before (PMID: 23318515, PMID: 24910390). It was classified as likely pathogenic (PS1, PM1, PM2, PM3).
GeneReviews RCV000192213 SCV000223798 not provided Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 no assertion provided literature only

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