ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.136A>G (p.Met46Val)

gnomAD frequency: 0.00001  dbSNP: rs1427310721
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001148069 SCV001308931 uncertain significance Neuronal ceroid lipofuscinosis 7 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001148069 SCV003524021 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-03-09 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 46 of the MFSD8 protein (p.Met46Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 31489614). ClinVar contains an entry for this variant (Variation ID: 901899). 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"). 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 RCV002559419 SCV003621895 uncertain significance Inborn genetic diseases 2022-05-20 criteria provided, single submitter clinical testing The c.136A>G (p.M46V) alteration is located in exon 3 (coding exon 2) of the MFSD8 gene. This alteration results from a A to G substitution at nucleotide position 136, causing the methionine (M) at amino acid position 46 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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