ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3971A>T (p.Asn1324Ile) (rs749820299)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000248590 SCV000320562 uncertain significance Cardiovascular phenotype 2015-12-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign)
GeneDx RCV000181381 SCV000233682 uncertain significance not provided 2017-08-30 criteria provided, single submitter clinical testing Although the N1324I variant of uncertain significance in the DSP gene has not been published as pathogenic or been reported as benign to our knowledge, it has been identified independently of additional cardiogenetic variants in one other individual referred for cardiomyopathy genetic testing at GeneDx; however, thus far, segregation data is limited or absent due to the lack of clinical information provided and/or insufficient participation by informative family members. The N1324I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N1324I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014).

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