ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.1394G>A (p.Arg465Gln)

gnomAD frequency: 0.00001  dbSNP: rs1275962600
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia RCV001263428 SCV001424316 likely pathogenic Neuronal ceroid lipofuscinosis 7 criteria provided, single submitter clinical testing
GeneDx RCV002272437 SCV002558418 likely pathogenic not provided 2022-01-11 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (Wang et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed with a pathogenic variant in a patient with variant late-infantile neuronal ceroid lipofuscinosis, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Kousi et al., 2012); Observed with a possible hypomorphic variant on the opposite allele (in trans) in three siblings with late-onset isolated maculopathy (Khan et al.; 2017); This variant is associated with the following publications: (PMID: 34910516, 28586915, 31741823, 30487145, 21990111, 33084218)
Invitae RCV001263428 SCV003525608 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 465 of the MFSD8 protein (p.Arg465Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MFSD-related conditions (PMID: 21990111, 28586915, 33084218). ClinVar contains an entry for this variant (Variation ID: 983438). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Revvity Omics, Revvity Omics RCV002272437 SCV003834010 likely pathogenic not provided 2021-12-10 criteria provided, single submitter clinical testing

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