ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.1535G>A (p.Arg512Lys)

gnomAD frequency: 0.00002  dbSNP: rs796052748
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188186 SCV000241793 uncertain significance not provided 2014-02-19 criteria provided, single submitter clinical testing p.Arg512Lys (AGA>AAA): c.1535 G>A in exon 13 of the MFSD8 gene (NM_152778.2)A variant of unknown significance has been identified in the MFSD8 gene. The Arg512Lys variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. However, the Arg512Lys variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001306456 SCV001495829 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-04-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 512 of the MFSD8 protein (p.Arg512Lys). This variant is present in population databases (rs796052748, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MFSD8-related conditions. ClinVar contains an entry for this variant (Variation ID: 206166). 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 tolerated. 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.
Natera, Inc. RCV001272729 SCV001454987 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2020-01-17 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.