ClinVar Miner

Submissions for variant NM_152594.3(SPRED1):c.1044_1046delinsC (p.Arg349fs) (rs1566876929)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000685042 SCV000812513 pathogenic Legius syndrome 2018-06-09 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides and inserts 1 nucleotide in exon 7 of the SPRED1 mRNA (c.1044_1046delinsC), resulting in a premature translational stop signal in the SPRED1 gene (p.Arg349Glyfs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 96 amino acids of the SPRED1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPRED1-related disease. However, a different variant (c.1045_1046del) giving rise to the same protein effect observed here (p.Arg349Glyfs*11) has been reported in individuals affected with Legius syndrome (PMID: 21089071, 21649642). A different truncation (p.Gly385Ilefs*20) that lies downstream of this variant has been determined to be pathogenic (PMID: 19920235, 19443465, 21089071, 17704776). This suggests that deletion of this region of the SPRED1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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