ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.541G>A (p.Val181Met) (rs148412181)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169209 SCV000220464 likely pathogenic Ceroid lipofuscinosis neuronal 1 2014-06-27 criteria provided, single submitter literature only
Invitae RCV000169209 SCV000958226 pathogenic Ceroid lipofuscinosis neuronal 1 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 181 of the PPT1 protein (p.Val181Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs148412181, ExAC 0.03%). This variant has been observed to segregate with neuronal ceroid lipofucinosis in several families (PMID: 22387303, 23374165). ClinVar contains an entry for this variant (Variation ID: 188857). Experimental studies have shown that this missense change results in loss of PPT enzyme activity in a neuroblastoma cell line (PMID: 28878621) as well as in patient lymphoblasts (PMID: 9664077, 11440996). Variants that disrupt the p.Val181 amino acid residue in PPT1 have been observed in affected individuals (PMID: 21499717, 19302939). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000169209 SCV000965817 pathogenic Ceroid lipofuscinosis neuronal 1 2016-01-04 criteria provided, single submitter clinical testing

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