ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.115A>G (p.Ile39Val)

dbSNP: rs201739608
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498574 SCV000589433 uncertain significance not provided 2019-01-08 criteria provided, single submitter clinical testing The I39V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I39V 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 I39V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species, and Valine has been seen at this position in evolution. 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 variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001239875 SCV001412777 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 39 of the MFSD8 protein (p.Ile39Val). This variant is present in population databases (rs201739608, gnomAD 0.007%). 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: 431874). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. RCV001273685 SCV001457015 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2019-11-11 no assertion criteria provided clinical testing

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