ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.6830G>A (p.Arg2277Gln) (rs200979896)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000726963 SCV000620708 uncertain significance not provided 2017-09-08 criteria provided, single submitter clinical testing The R2277Q variant has not been published as pathogenic or been reported as benign to our knowledge. The R2277Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to)] the protein structure/function. The Exome Aggregation Consortium reports R2277Q was observed in 21/11,468 (0.2%) alleles from individuals of Latino background (Lek et al., 2016).
Invitae RCV000545359 SCV000631797 uncertain significance Alstrom syndrome 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2277 of the ALMS1 protein (p.Arg2277Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200979896, ExAC 0.2%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 451941). 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: "Tolerated"; PolyPhen-2: "Probably 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726963 SCV000704510 uncertain significance not provided 2016-12-29 criteria provided, single submitter clinical testing

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