Submissions for variant NM_004415.4(DSP):c.2T>G (p.Met1Arg) (rs748738880)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493448	SCV000582174	likely pathogenic	not provided	2018-03-30	criteria provided, single submitter	clinical testing	The c.2 T>G variant has not been published as a pathogenic or reported as a benign variant to our knowledge. The c.2 T>G variant was not observed in approximately 6400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is predicted to alter the initiator Methionine codon, and the resultant protein would be described as p.Met1?" using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. Other truncating and missense pathogenic variants have been reported in the Human Gene Mutation Database in association with cardiomyopathy or DSP-related disorder (Stenson et al., 2014), supporting the functional importance of this region of the protein.Therefore, this variant is likely pathogenic; however, additional information is required to determine the clinical significance of this variant."