ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.325T>G (p.Tyr109Asp) (rs386833642)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188711 SCV000242335 pathogenic not provided 2013-08-07 criteria provided, single submitter clinical testing p.Tyr109Asp (TAC>GAC): c.325 T>G in exon 3 of the PPT1 gene (NM_000310.3). The Tyr109Asp mutation has been previously reported in multiple individuals with neuronal ceroid lipofuscinosis (NCL) who harbored a second mutation on the other allele (Das et al., 1998; Kousi et al., 2011). This mutation is a non-conservative amino acid substitution of an uncharged Tyrosine residue with a negatively charged Aspartic acid residue at a position that is conserved across species, and functional studies indicate that it results in significantly impaired enzyme activity (Das et al., 2001). Therefore, Tyr109Asp is considered a disease-causing mutation. The variant is found in EPILEPSY panel(s).
Invitae RCV000049601 SCV001219531 likely pathogenic Neuronal ceroid lipofuscinosis 1 2019-09-18 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with aspartic acid at codon 109 of the PPT1 protein (p.Tyr109Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. This variant is present in population databases (rs386833642, ExAC 0.001%). This variant has been observed in several individuals affected with neuronal ceroid lipofuscinosis (PMID: 9664077, 10191107, 21990111). ClinVar contains an entry for this variant (Variation ID: 56190). This variant has been reported to affect PPT1 protein function (PMID: 11440996). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049601 SCV000082008 probable-pathogenic Neuronal ceroid lipofuscinosis 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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