ClinVar Miner

Submissions for variant NM_020778.5(ALPK3):c.3340C>T (p.Arg1114Ter)

gnomAD frequency: 0.00001  dbSNP: rs751041696
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001928540 SCV002179527 pathogenic not provided 2024-03-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1316*) in the ALPK3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPK3 are known to be pathogenic (PMID: 21441111, 26846950, 27106955, 34263907). This variant is present in population databases (rs751041696, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALPK3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1414127). For these reasons, this variant has been classified as Pathogenic.
3billion, Medical Genetics RCV003152778 SCV003842018 pathogenic Cardiomyopathy, familial hypertrophic 27 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with ALPK3 related disorder (ClinVar ID: VCV001414127). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Ambry Genetics RCV003167169 SCV003854077 pathogenic Cardiovascular phenotype 2023-03-01 criteria provided, single submitter clinical testing The p.R1316* pathogenic mutation (also known as c.3946C>T), located in coding exon 6 of the ALPK3 gene, results from a C to T substitution at nucleotide position 3946. This changes the amino acid from an arginine to a stop codon within coding exon 6. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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