ClinVar Miner

Submissions for variant NM_005506.4(SCARB2):c.1328T>C (p.Met443Thr) (rs141250135)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727505 SCV000242428 uncertain significance not provided 2014-01-20 criteria provided, single submitter clinical testing p.Met443Thr (ATG>ACG): c.1328 T>C in exon 11 of the SCARB2 gene (NM_005506.3) The Met443Thr missense change in the SCARB2 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. This variant is a non-conservative amino acid substitution of a non-polar Methionine residue with a polar Threonine residue at a position that is conserved across species. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Met443Thr is a disease-causing mutation or a rare benign variant.The variant is found in EPILEPSY panel(s).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727505 SCV000709257 uncertain significance not provided 2017-06-12 criteria provided, single submitter clinical testing
Invitae RCV000819871 SCV000960554 uncertain significance Progressive myoclonic epilepsy 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 443 of the SCARB2 protein (p.Met443Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs141250135, ExAC 0.02%). This variant has not been reported in the literature in individuals with SCARB2-related disease. ClinVar contains an entry for this variant (Variation ID: 206717). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). 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.

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