ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.8489G>A (p.Cys2830Tyr) (rs369720907)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001204808 SCV001376031 uncertain significance Alstrom syndrome 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 2831 of the ALMS1 protein (p.Cys2831Tyr). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs369720907, ExAC 0.002%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The tyrosine 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 and their clinical significance is uncertain. 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.
GeneDx RCV001578191 SCV001805732 uncertain significance not provided 2019-11-08 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

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