ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.11032C>T (p.Arg3678Trp) (rs766771102)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000437171 SCV000525390 uncertain significance not specified 2016-03-01 criteria provided, single submitter clinical testing The R3679W variant in the ALMS1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R3679W variant was not observed in approximately 5900 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 R3679W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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. We interpret R3679W as a variant of uncertain significance.
Counsyl RCV000665868 SCV000790059 uncertain significance Alstrom syndrome 2017-04-14 criteria provided, single submitter clinical testing
Invitae RCV000665868 SCV001497498 uncertain significance Alstrom syndrome 2020-10-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 3679 of the ALMS1 protein (p.Arg3679Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs766771102, ExAC 0.01%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 384519). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Natera, Inc. RCV000665868 SCV001455020 uncertain significance Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing

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