ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.883G>A (p.Glu295Lys) (rs121434286)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000055839 SCV000965804 pathogenic Juvenile neuronal ceroid lipofuscinosis 2015-01-01 criteria provided, single submitter clinical testing
GeneReviews RCV000055839 SCV000086831 pathologic Juvenile neuronal ceroid lipofuscinosis 2013-08-01 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000811923 SCV000952214 pathogenic Neuronal ceroid lipofuscinosis 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 295 of the CLN3 protein (p.Glu295Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs121434286, ExAC 0.003%). This variant has been observed to segregate with cone rod dystrophy and neuronal ceroid lipofuscinosis in families and individuals (PMID: 24154662, 9450775, 9311735, 27486012 ). ClinVar contains an entry for this variant (Variation ID: 3556). Experimental studies in yeast cells and mouse neuronal cells have shown that this missense change causes increased vacoular size, slower trafficking through the prevacuolar compartments, can rescue the survival phenotype by rescuing vacuolar pH, has the same subcellular localization as wild type cells and is able to move along axons toward the neuronal plate same as wild type suggesting that this variant has a very mild effect on protein function (PMID: 10332042, 16291725, 19132115). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003735 SCV000023898 pathogenic Ceroid lipofuscinosis, neuronal, 3, protracted 1998-01-01 no assertion criteria provided literature only

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