ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.889A>C (p.Met297Leu)

dbSNP: rs1419909769
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522949 SCV000621302 uncertain significance not provided 2017-09-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MFSD8 gene. The M297L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M297L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The M297L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and 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 variant or a rare benign variant.
Invitae RCV001302138 SCV001491332 uncertain significance Neuronal ceroid lipofuscinosis 7 2020-06-06 criteria provided, single submitter clinical testing 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MFSD8-related conditions. ClinVar contains an entry for this variant (Variation ID: 452491). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with leucine at codon 297 of the MFSD8 protein (p.Met297Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine.

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