ClinVar Miner

Submissions for variant NM_005506.4(SCARB2):c.1136C>T (p.Ala379Val) (rs144147706)

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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 RCV000724109 SCV000233093 uncertain significance not provided 2014-10-06 criteria provided, single submitter clinical testing
Invitae RCV000471428 SCV000545819 uncertain significance Progressive myoclonic epilepsy 2018-04-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 379 of the SCARB2 protein (p.Ala379Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs144147706, ExAC 0.03%). This variant has not been reported in the literature in individuals with SCARB2-related disease. ClinVar contains an entry for this variant (Variation ID: 199108). 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: "Possibly 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.
GeneDx RCV000724109 SCV000621945 uncertain significance not provided 2018-06-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCARB2 gene. The A379V variant hasnot been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 13/24032 (0.05%) alleles from individuals of Africanbackground, in large population cohorts (Lek et al., 2016). The A379V variant is a conservativeamino acid substitution, which is not likely to impact secondary protein structure as these residuesshare similar properties. This substitution occurs at a position where amino acids with similarproperties to Alanine are tolerated across species. In silico analysis is inconsistent in its predictions asto whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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