ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.1639C>G (p.Leu547Val)

gnomAD frequency: 0.00001  dbSNP: rs1451493287
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803905 SCV000943793 uncertain significance Alstrom syndrome 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 548 of the ALMS1 protein (p.Leu548Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALMS1-related disease. 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 valine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Fulgent Genetics, Fulgent Genetics RCV000803905 SCV002803977 uncertain significance Alstrom syndrome 2021-12-16 criteria provided, single submitter clinical testing
Natera, Inc. RCV000803905 SCV002080422 uncertain significance Alstrom syndrome 2020-09-24 no assertion criteria provided clinical testing

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