ClinVar Miner

Submissions for variant NM_001042432.2(CLN3):c.1A>G (p.Met1Val)

gnomAD frequency: 0.00001  dbSNP: rs386833708
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664968 SCV000789014 likely pathogenic Neuronal ceroid lipofuscinosis 3 2016-12-27 criteria provided, single submitter clinical testing
Invitae RCV001868197 SCV002234992 pathogenic Neuronal ceroid lipofuscinosis 2023-12-19 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the CLN3 mRNA. The next in-frame methionine is located at codon 55. This variant is present in population databases (rs386833708, gnomAD 0.006%). Disruption of the initiator codon has been observed in individuals with Neuronal ceroid lipofuscinosis and/or retinitis pigmentosa (PMID: 32154056; Invitae). ClinVar contains an entry for this variant (Variation ID: 550268). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003420170 SCV004107270 likely pathogenic CLN3-related disorder 2023-04-28 criteria provided, single submitter clinical testing The CLN3 c.1A>G variant is predicted to disrupt the translation initiation site (Start loss). This variant has not been reported in the literature, however other variant c.1A>C disrupting initiation codon has been reported in compound heterozygous state in three individuals with attenuated form of CLN3 disease (Kuper et al 2020. PubMed ID: 32154056). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-28503080-T-C). In summary, we interpret this variant as likely pathogenic.

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