Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313681 | SCV000848910 | uncertain significance | Inborn genetic diseases | 2017-02-03 | criteria provided, single submitter | clinical testing | The p.R35Q variant (also known as c.104G>A), located in coding exon 2 of the MFSD8 gene, results from a G to A substitution at nucleotide position 104. The arginine at codon 35 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Labcorp Genetics |
RCV001862043 | SCV002111987 | uncertain significance | Neuronal ceroid lipofuscinosis 7 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 35 of the MFSD8 protein (p.Arg35Gln). This variant is present in population databases (rs146596875, gnomAD 0.002%). 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: 588744). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Mendelics | RCV002249438 | SCV002518240 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002249438 | SCV005381375 | uncertain significance | not specified | 2024-08-06 | criteria provided, single submitter | clinical testing | Variant summary: MFSD8 c.104G>A (p.Arg35Gln) results in a conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250812 control chromosomes. c.104G>A has been reported in the literature in at-least two individuals affected with adult-onset neuronal ceroid lipofuscinosis type 7 (He_2023)and Teenage-onset cone dystrophy, in which the variant was in cis with another VUS missense and in trans with a nonsense varint in MFSD8 (Poncet_2022). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36972931, 35457110). ClinVar contains an entry for this variant (Variation ID: 588744). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Natera, |
RCV001830591 | SCV002084811 | uncertain significance | Late-infantile neuronal ceroid lipofuscinosis | 2021-07-13 | no assertion criteria provided | clinical testing |