ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.569dup (p.Ala191fs) (rs386833732)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540211 SCV000628934 pathogenic Neuronal ceroid lipofuscinosis 2017-03-10 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 9 of the CLN3 mRNA (c.569dupG), causing a frameshift at codon 191. This creates a premature translational stop signal (p.Ala191Serfs*45) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001008369 SCV001168137 pathogenic not provided 2018-09-26 criteria provided, single submitter clinical testing The c.569dupG variant in the CLN3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.569dupG variant causes a frameshift starting with codon Alanine 191, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 45 of the new reading frame, denoted p.Ala191SerfsX45. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.569dupG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.569dupG as a pathogenic variant.

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