ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.5276A>G (p.Tyr1759Cys) (rs200293447)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000616627 SCV000713771 uncertain significance not specified 2017-12-05 criteria provided, single submitter clinical testing The p.Tyr1758Cys variant in ALMS1 has not been previously reported in individual s with hearing loss or Alstrom syndrome, but has been identified in 0.05% (11/24 000) of African chromosomes by the Genome Aggregation Database (gnomAD, http://g; dbSNP rs200293447). Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, tho ugh this information is not predictive enough to rule out pathogenicity. In summ ary, the clinical significance of the p.Tyr1758Cys variant is uncertain. ACMG/AM P Criteria applied: BP4.
Invitae RCV001247712 SCV001421151 uncertain significance Alstrom syndrome 2019-05-17 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1760 of the ALMS1 protein (p.Tyr1760Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs200293447, ExAC 0.09%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 506220). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.

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