ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.8647C>T (p.Leu2883Phe) (rs373944325)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000422228 SCV000534912 uncertain significance not provided 2018-04-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The L2883F variant has not been published as pathogenic or been reported as benign to our knowledge. This substitution occurs at a position that is conserved in mammals. However, the L2883F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Finally, the L2883F variant is observed in 28/126,330 alleles from individuals of European (Non-Finnish) ancestry in the large population cohorts (Lek et al., 2016).
Invitae RCV000811073 SCV000951320 uncertain significance Alstrom syndrome 2018-08-30 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 2883 of the ALMS1 protein (p.Leu2883Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs373944325, ExAC 0.02%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 391768). 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: "Tolerated"; PolyPhen-2: "Not Available"; 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.

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