ClinVar Miner

Submissions for variant NM_152778.3(MFSD8):c.1141G>T (p.Glu381Ter) (rs724159970)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481423 SCV000568390 pathogenic not provided 2017-03-24 criteria provided, single submitter clinical testing The E381X nonsense variant in the MFSD8 gene has been reported previously in an individual with seizures and electron microscopy showing fingerprint profiles and curvilinear bodies who also had a second MFSD8 nonsense variant identified (Aiello et al., 2009). The E381X variant has also been reported in a family with macular dystrophy who had a second MFSD8 missense variant identified; however, none of the affected individuals had any symptoms of neural ceroid lipofuscinosis (NCL) (Roosing et al., 2015). The E381X pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV000149772 SCV001408307 pathogenic Neuronal ceroid lipofuscinosis 7 2019-11-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu381*) in the MFSD8 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs724159970, ExAC 0.001%). This variant has been observed in individual(s) with neuronal ceroid lipofuscinoses and macular dystrophy with central cone involvement (PMID: 19177532, 25227500). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162379). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in MFSD8 are known to be pathogenic (PMID: 19177532, 25227500, 28586915). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000149772 SCV000196585 pathogenic Neuronal ceroid lipofuscinosis 7 2015-01-01 no assertion criteria provided literature only
OMIM RCV000149773 SCV000196586 pathogenic Macular dystrophy with central cone involvement 2015-01-01 no assertion criteria provided literature only

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