ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.832G>A (p.Val278Met)

gnomAD frequency: 0.00001  dbSNP: rs796052743
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188174 SCV000241781 uncertain significance not provided 2014-02-21 criteria provided, single submitter clinical testing p.Val278Met (GTG>ATG): c.832 G>A in exon 9 of the MFSD8 gene (NM_152778.2)A variant of unknown significance has been identified in the MFSD8 gene. The Val278Met 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. The Val278Met variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, this substitution occurs at a position in the transmembrane domain of the MFSD8 protein that is not conserved across all species, nor have nearby missense mutations been reported in the literature to our knowledge. However, in silico analysis predicts this variant is probably 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 INFANT-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000695060 SCV000823536 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-06-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 278 of the MFSD8 protein (p.Val278Met). This variant is present in population databases (rs796052743, gnomAD 0.02%). 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: 206155). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002433848 SCV002677148 uncertain significance Inborn genetic diseases 2019-04-25 criteria provided, single submitter clinical testing The p.V278M variant (also known as c.832G>A), located in coding exon 8 of the MFSD8 gene, results from a G to A substitution at nucleotide position 832. The valine at codon 278 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001272736 SCV001454994 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2020-03-17 no assertion criteria provided clinical testing

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