ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.611A>C (p.Glu204Ala) (rs200054604)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234342 SCV000290098 uncertain significance Alstrom syndrome 2020-09-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with alanine at codon 205 of the ALMS1 protein (p.Glu205Ala). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. This variant is present in population databases (rs200054604, ExAC 0.1%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 241006). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, Align-GVGD) suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional 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.
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000445446 SCV000536960 likely benign Monogenic diabetes 2018-11-21 criteria provided, single submitter research ACMG criteria: BP4 (REVEL 0.110 + 6 predictors), BP1 (missense in gene where truncating cause disease)= Likely benign *Note: some descrepancy in the c. and p.nomenclatures based on NM version changes(c.611 vs c.614 and p.204 vs p.205)
GeneDx RCV001762541 SCV002000740 uncertain significance not provided 2021-10-19 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar (ClinVar Variant ID# 241006; Landrum et al., 2016)
Natera, Inc. RCV000234342 SCV001453435 uncertain significance Alstrom syndrome 2019-11-11 no assertion criteria provided clinical testing

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