ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.652G>A (p.Ala218Thr)

gnomAD frequency: 0.00003  dbSNP: rs368614789
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188170 SCV000241777 uncertain significance not provided 2012-06-11 criteria provided, single submitter clinical testing p.Ala218Thr (GCC>ACC): c.652 G>A in exon 7 of the MFSD8 gene (NM_152778.2)The Ala218Thr missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid substitution is non-conservative, as a non-polar Alanine residue is replaced by a polar Threonine residue, and it alters a highly conserved position in the sixth transmembrane domain of the protein. Multiple in siliso algorithms predict Ala218Thr may be damaging to protein structure/function, although another model predicts it is likely not pathogenic. Therefore, based on the currently available information, it is unclear whether Ala218Thr is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001244551 SCV001417779 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-07-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 218 of the MFSD8 protein (p.Ala218Thr). This variant is present in population databases (rs368614789, gnomAD 0.02%). 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: 206152). 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.
Ambry Genetics RCV002362983 SCV002660176 uncertain significance Inborn genetic diseases 2023-05-09 criteria provided, single submitter clinical testing The c.652G>A (p.A218T) alteration is located in exon 7 (coding exon 6) of the MFSD8 gene. This alteration results from a G to A substitution at nucleotide position 652, causing the alanine (A) at amino acid position 218 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002485272 SCV002792965 uncertain significance Neuronal ceroid lipofuscinosis 7; Macular dystrophy with central cone involvement 2021-07-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001833121 SCV002084790 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2019-11-11 no assertion criteria provided clinical testing

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