ClinVar Miner

Submissions for variant NM_004572.3(PKP2):c.1440_1444del (p.Asn480fs) (rs775995156)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483764 SCV000568236 likely pathogenic not provided 2017-07-12 criteria provided, single submitter clinical testing This five base pair deletion has been reported previously in the Human Gene Mutation Database and the Arrhythmogenic Right Ventricular Cardiomyopathy database (Stenson et al., 2014; Van et al., 2009). The c.1440_1444delTCCCA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant causes a shift in reading frame starting at codon Asparagine 480, changing it to a Lysine, and creating a premature stop codon at position 20 of the new reading frame, denoted p.Asn480LysfsX20. This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the PKP2 gene have been reported in HGMD in association with ARVC (Stenson et al., 2014).
Invitae RCV001069896 SCV001235094 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 9 2019-03-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn480Lysfs*20) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 25157032). ClinVar contains an entry for this variant (Variation ID: 419977). Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). For these reasons, this variant has been classified as Pathogenic.
Color RCV001184322 SCV001350273 uncertain significance Cardiomyopathy 2019-01-10 criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000483764 SCV000809447 pathogenic not provided 2018-09-16 no assertion criteria provided research

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