ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.11414G>C (p.Arg3805Thr) (rs201028172)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434442 SCV000533350 uncertain significance not provided 2018-09-24 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The R3805T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R3805T variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to 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 pathogenic or benign.
Invitae RCV000548287 SCV000631757 uncertain significance Alstrom syndrome 2017-12-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 3805 of the ALMS1 protein (p.Arg3805Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs201028172, ExAC 0.05%) but has not been reported in the literature in individuals with a ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 390504). 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 C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it 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.
Fulgent Genetics,Fulgent Genetics RCV000548287 SCV000897048 uncertain significance Alstrom syndrome 2018-10-31 criteria provided, single submitter clinical testing

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