ClinVar Miner

Submissions for variant NM_014254.3(RXYLT1):c.970C>T (p.Gln324Ter) (rs1555228198)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556292 SCV000653003 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 2017-03-09 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the TMEM5 mRNA at codon 324 (p.Gln324*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 120 amino acids of the TMEM5 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TMEM5-related disease. Multiple downstream truncations have been reported in individuals affected with severe dystroglycanopathy (PMID: 23519211, 23217329). This suggests that deletion of this region of the TMEM5 protein is causative of disease. In summary, this variant is a rare truncation located in the last exon of TMEM5 upstream of truncations that have been reported in affected individuals. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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