ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5522C>T (p.Ser1841Leu) (rs397516947)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038066 SCV000061732 uncertain significance not specified 2012-11-28 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ser1841Leu vari ant in DSP has not been reported in the literature nor previously identified by our laboratory. This variant has not been identified in large and broad European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/), though it remains possible that this varia nt is common in other populations. Serine (Ser) at position 1841 is not conserve d in evolution and several species (fish) carry the variant amino acid, suggesti ng that this change may be tolerated. In summary, the lack of conservation suppo rts that the Ser1841Leu variant may be benign, but additional studies are needed to fully assess its clinical significance.
GeneDx RCV000766555 SCV000577389 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing The S1841L variant of uncertain significance in the DSP gene has not been published as pathogenic or been reported as benign to our knowledge. S1841L has been observed in 5/16,500 (0.03%) alleles from individuals of South Asian ancestry in the Exome Aggregation Consortium (Lek et al., 2016). The S1841L 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. However, this substitution occurs at a position that is not conserved, where L1841 is the wild-type residue in multiple species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

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