ClinVar Miner

Submissions for variant NM_198586.3(NHLRC1):c.528C>G (p.Tyr176Ter) (rs1403101337)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Institute Rare Disease Group,Broad Institute RCV001004859 SCV001164337 likely pathogenic Lafora disease 2018-12-03 criteria provided, single submitter research The homozygous p.Tyr176Ter variant in NHLRC1 was identified by our study in two siblings with myoclonic epilepsy of lafora. The p.Tyr176Ter variant in NHLRC1 has not been previously reported in individuals with myoclonic epilepsy of lafora and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 176. This alteration occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Loss of function of the NHLRC1 gene is an established disease mechanism in autosomal recessive myoclonic epilepsy of lafora. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1_Strong (Richards 2015).

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