ClinVar Miner

Submissions for variant NM_005506.4(SCARB2):c.379G>T (p.Asp127Tyr) (rs148022786)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000728594 SCV000856186 uncertain significance not provided 2017-08-17 criteria provided, single submitter clinical testing
GeneDx RCV000728594 SCV000618282 uncertain significance not provided 2018-12-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCARB2 gene. The D127Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 19/24030 (0.08%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The D127Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000638322 SCV000759816 uncertain significance Progressive myoclonic epilepsy 2017-10-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 127 of the SCARB2 protein (p.Asp127Tyr). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs148022786, ExAC 0.08%). This variant has not been reported in the literature in individuals with SCARB2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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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