Submissions for variant NM_004415.4(DSP):c.6398dup (p.Val2134fs)

dbSNP: rs794728147

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181370	SCV000233671	pathogenic	not provided	2013-07-11	criteria provided, single submitter	clinical testing	Although the c.6398dupG mutation in the DSP gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at codon Valine 2134, changing it to a Cysteine, and creating a premature stop codon at position 22 of the new reading frame, denoted p.Val2134CysfsX22. This mutation is expected to result in an abnormal, truncated protein product. Other frameshift mutations in the DSP gene have been reported in association with ARVC. The variant is found in ARVC panel(s).
Invitae	RCV001385911	SCV001585929	pathogenic	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2020-03-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the DSP protein. Other variant(s) that disrupt this region (p.Ile2359Serfs*10) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 199926). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the DSP gene (p.Val2134Cysfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 738 amino acids of the DSP protein.