ClinVar Miner

Submissions for variant NM_005506.4(SCARB2):c.1271G>A (p.Arg424Gln) (rs751827409)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656972 SCV000242415 uncertain significance not provided 2018-10-24 criteria provided, single submitter clinical testing The R424Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R424Q variant is observed in 59/34418 (0.2%) alleles from individuals of Latino background (Lek et al., 2016). The R424Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000656972 SCV000342328 uncertain significance not provided 2016-06-17 criteria provided, single submitter clinical testing
Invitae RCV000457928 SCV000545817 uncertain significance Progressive myoclonic epilepsy 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 424 of the SCARB2 protein (p.Arg424Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs751827409, ExAC 0.2%) but has not been reported in the literature in individuals with a SCARB2-related disease. ClinVar contains an entry for this variant (Variation ID: 206705). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000718564 SCV000849428 uncertain significance Seizures 2017-04-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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