ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.34C>T (p.Pro12Ser)

gnomAD frequency: 0.00004  dbSNP: rs371882083
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188162 SCV000241769 uncertain significance not provided 2018-07-03 criteria provided, single submitter clinical testing p.Pro12Ser (CCG>TCG): c.34 C>T in exon 2 of the MFSD8 gene (NM_152778.2)A variant of unknown significance has been identified in the MFSD8 gene. The P12S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The P12S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P12S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across mammals. However, 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 CHILD-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001852475 SCV002118785 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 12 of the MFSD8 protein (p.Pro12Ser). This variant is present in population databases (rs371882083, gnomAD 0.006%). 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: 206145). 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: "Possibly 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.
Natera, Inc. RCV001828002 SCV002084815 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2019-10-28 no assertion criteria provided clinical testing

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