ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.4196dup (p.Ser1400fs) (rs730880370)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766287 SCV000710229 uncertain significance not provided 2017-12-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ABCC9 gene. The c.4196dupT variant has not been published as pathogenic or been reported as benign to our knowledge. The c.4196dupT variant is not observed in large population cohorts (Lek et al., 2016). This variant causes a shift in reading frame starting at codon serine 1400, changing it to a glutamine, and creating a premature stop codon at position 5 of the new reading frame, denoted p.Ser1400GlnfsX5. 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. However, only a few loss of function variants in the PRDM16 gene have been reported in Human Gene Mutation Database in association with ABCC9-related disorders (Stenson et al., 2014), indicating that loss of function is not an established mechanism of disease for this gene.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156786 SCV000206507 uncertain significance not specified 2014-08-27 criteria provided, single submitter clinical testing The Ser1400fs variant in ABCC9 has not been previously reported in individuals w ith cardiomyopathy or in large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 1400 and leads to a premature termination codon 5 amino acids downstrea m. This alteration is then predicted to lead to a truncated or absent protein. A lthough this variant is predicted to be deleterious to the protein, the variant spectrum of this gene has not been well characterized and it is unclear if varia nts of this type play a role in disease. In summary, the clinical significance o f the Ser1400fs variant is uncertain.

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