ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs748738880
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493448 SCV000582174 uncertain significance not provided 2022-08-17 criteria provided, single submitter clinical testing Reported previously by whole-exome sequencing in 1 of 61,019 individuals in the DiscovEHR cohort, with no indication of cardiomyopathy from the electronic health record of that individual (Carruth et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31638835)
Invitae RCV001204253 SCV001375452 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-10-03 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the DSP mRNA. The next in-frame methionine is located at codon 17. This variant is present in population databases (rs748738880, gnomAD 0.002%). Disruption of the initiator codon has been observed in individual(s) with clinical features of DSP-related conditions (PMID: 31317183). ClinVar contains an entry for this variant (Variation ID: 429571). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV001524186 SCV001733964 uncertain significance Cardiomyopathy 2023-06-13 criteria provided, single submitter clinical testing This variant results in the loss of the translation initiation codon methionine (p.Met1?) of the DSP gene. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy (PMID: 31317183). This variant has been identified in 2/233270 chromosomes in the general population by the Genome Aggregation Database (gnomAD). While loss of DSP function is a known mechanism of disease, one cannot rule out the possibility that a downstream in-frame methionine may be used for alternate protein translation initiation and lead to the production of functional protein. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics RCV002248722 SCV002516994 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing

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