ClinVar Miner

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

gnomAD frequency: 0.00004  dbSNP: rs750502331
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Total submissions: 5
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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 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 4096 of the ALMS1 protein (p.Pro4096Leu). This variant is present in population databases (rs750502331, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected 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: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 2023-09-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002360697 SCV002663846 uncertain significance Cardiovascular phenotype 2021-02-09 criteria provided, single submitter clinical testing The p.P4096L variant (also known as c.12287C>T), located in coding exon 20 of the ALMS1 gene, results from a C to T substitution at nucleotide position 12287. The proline at codon 4096 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000668351 SCV002081410 uncertain significance Alstrom syndrome 2021-06-30 no assertion criteria provided clinical testing

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