ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.12284C>T (p.Pro4095Leu) (rs750502331)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668351 SCV000792933 uncertain significance Alstrom syndrome 2017-07-24 criteria provided, single submitter clinical testing
Invitae RCV000668351 SCV001416241 uncertain significance Alstrom syndrome 2019-01-15 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 4096 of the ALMS1 protein (p.Pro4096Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs750502331, ExAC 0.009%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 552991). 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 leucine 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 RCV001584539 SCV001820059 uncertain significance not provided 2019-07-29 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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