ClinVar Miner

Submissions for variant NM_152778.3(MFSD8):c.1444C>T (p.Arg482Ter) (rs724159971)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256110 SCV000322271 pathogenic not provided 2017-11-16 criteria provided, single submitter clinical testing The R482X pathogenic variant in the MFSD8 gene has been reported previously in association with variant late-infantile neuronal ceroid lipofucinosis (Aiello et al., 2009; Kousi et al., 2012). This variant is predicted to cause loss of normal protein function through protein truncation. The R482X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R482X as a pathogenic variant.
Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement,Assistance Publique Hopitaux de Paris RCV000149777 SCV000586765 pathogenic Neuronal ceroid lipofuscinosis 7 2017-01-06 criteria provided, single submitter clinical testing peripheric neuropathy; global cerebral atrophy; epilepsy (myoclonia); severe regression of acquisitions starting at 3 years old
Invitae RCV000149777 SCV000762058 pathogenic Neuronal ceroid lipofuscinosis 7 2019-10-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MFSD8 gene (p.Arg482*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 37 amino acids of the MFSD8 protein. This variant is present in population databases (rs724159971, ExAC 0.002%). This variant has been reported in multiple individuals affected with neuronal ceroid lipofuscinosis (PMID: 25976102, 28708303) and has been observed to segregate with disease in one affected family (Invitae). This variant has also been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with variant-late infantile neuronal ceroid lipofuscinosis (VL-NCL) (PMID: 19177532). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 162382). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763521 SCV000894333 likely pathogenic Neuronal ceroid lipofuscinosis 7; Macular dystrophy with central cone involvement 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000149777 SCV000196590 pathogenic Neuronal ceroid lipofuscinosis 7 2009-03-01 no assertion criteria provided literature only

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