ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.9148A>G (p.Ile3050Val) (rs202228570)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705169 SCV000834154 uncertain significance Alstrom syndrome 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 3050 of the ALMS1 protein (p.Ile3050Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoelucine and valine. This variant is present in population databases (rs202228570, ExAC 0.03%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Fulgent Genetics,Fulgent Genetics RCV000705169 SCV000897046 uncertain significance Alstrom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001195365 SCV001365711 uncertain significance not specified 2019-10-04 criteria provided, single submitter clinical testing The p.Ile3048Val variant in ALMS1 has not been previously reported in individuals with Alstrom syndrome, but has been identified in 0.1% (11/10354) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: BS1_Supporting.

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