ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.11356A>G (p.Ile3786Val) (rs201819880)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233166 SCV000290066 uncertain significance Alstrom syndrome 2019-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 3786 of the ALMS1 protein (p.Thr3786Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs201819880, ExAC 0.07%) but has not been reported in the literature in individuals with a ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 240977). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000437494 SCV000510803 uncertain significance not provided 2016-11-02 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000233166 SCV000897047 uncertain significance Alstrom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825109 SCV000966363 likely benign not specified 2018-06-25 criteria provided, single submitter clinical testing p.Ile3786Val in exon 16 of ALMS1: This variant is classified as likely benign be cause it has been identified in 0.08% (108/126020) of European chromosomes by th e Genome Aggregation Database (gnomAD,; dbSNP r s201819880) and computational prediction tools do not suggest a high likelihood of impact to the protein. ACMG/AMP Criteria applied: BS1_Supporting, BP4.

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