ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.597C>A (p.Tyr199Ter) (rs267606737)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169443 SCV000220861 likely pathogenic Juvenile neuronal ceroid lipofuscinosis 2014-11-06 criteria provided, single submitter literature only
GeneDx RCV000760368 SCV000890231 pathogenic not provided 2019-01-03 criteria provided, single submitter clinical testing The Y199X nonsense variant in the CLN3 gene has been reported previously in the homozygous state in five siblings with juvenile neuronal ceroid lipofuscinosis (Sarpong et al., 2009). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y199X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Therefore, Y199X is considered a pathogenic variant.
Invitae RCV000823290 SCV000964144 pathogenic Neuronal ceroid lipofuscinosis 2019-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr199*) in the CLN3 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs267606737, ExAC 0.002%). This variant has been observed in individual(s) with protracted juvenile neuronal ceroid lipofuscinosis (PMID: 19489875, 22013180). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3557). Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000760368 SCV001143613 pathogenic not provided 2018-11-14 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity. Very strong co-segregation with disease in affected individuals from a single family.
OMIM RCV000003736 SCV000023899 pathogenic Ceroid lipofuscinosis, neuronal, 3, protracted 2009-07-01 no assertion criteria provided literature only

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