ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8529_8540del (p.2827_2830SGSR[4]) (rs794728151)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181375 SCV000233676 uncertain significance not specified 2014-05-21 criteria provided, single submitter clinical testing The c.8529_8540del variant in the DSP gene has been reported previously as a variant of unknown significance in a patient with DCM, however this patient also harbors several other variants in several other cardiomyopathy-related genes (Pugh T et al., 2014). In addition, the 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. However, this variant has been reported with a frequency of 0.1%, 1/854 alleles, in healthy control individuals (Kapplinger J et al., 2011). This variant results in deletion of 12 nucleotides beginning at Arginine 2846 and does not causes a shift in reading frame. Only one other non-frameshift mutation in the DSP gene has been reported in association with ARVC.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000528276 SCV000641359 likely benign Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-12-09 criteria provided, single submitter clinical testing
Color RCV000777828 SCV000913826 likely benign Cardiomyopathy 2018-10-29 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000181375 SCV000280097 uncertain significance not specified 2014-03-27 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. Given that the variant is novel, and the type of variant we consider this variant a varian of uncertain significance. Variants in DSP have been associated with cardiomyopathy, primarily ARVC but also some cases of DCM (which may be left-sided ARVC). To our knowledge, the variant is novel. This is an in-frame deletion of four amino acids. Only one in-frame deletion has been reported before in associated with ARVC in HGMD. A neighboring in-frame deletion of the same size (p.Ser2843_Arg2846del) was observed in 1 of 427 "ostensibly healthy" controls studied by Kapplinger et al (2011) and a patient with DCM in the LMM cohort who also carried variants in MYH6, TTN, ABCC9, DSG2, and MYL3 (Pugh et al 2014). This variant is not listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6500 Caucasian and African American individuals (as of July 28th, 2014). However, this is not a reliable dataset for multi-nucleotide insertions or deletions. There variant is not listed in dbSNP (as of July 29th, 2014).

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