ClinVar Miner

Submissions for variant NM_020778.4(ALPK3):c.4332del (p.Lys1445fs) (rs745688425)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000607554 SCV000711734 likely pathogenic Hypertrophic cardiomyopathy 2018-01-23 criteria provided, single submitter clinical testing The p.Lys1445fs variant in ALPK3 has not been previously reported in individuals with cardiomyopathy, but was identified in 2/76928 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). This var iant is predicted to cause a frameshift, which alters the protein?s amino acid s equence beginning at position 1445 and leads to a premature termination codon 29 amino acids downstream. This alteration is then predicted to lead to a truncate d or absent protein. Biallelic loss-of-function (LOF) variants in the ALPK3 gene have been reported in multiple individuals and a mouse model with cardiomyopath y (HCM or mixed HCM/DCM; Almomani 2016, Phelan 2016, Van Sligtenhorst 2012). In summary, although additional studies are required to fully establish its clinica l significance, the p.Lys1445fs variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1_Strong.

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