ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4601A>G (p.Tyr1534Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001373835 SCV001570567 uncertain significance Alstrom syndrome 2020-08-06 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1535 of the ALMS1 protein (p.Tyr1535Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs751003573, ExAC 0.001%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001553711 SCV001774688 uncertain significance not specified 2021-07-19 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.4598A>G (p.Tyr1533Cys) results in a non-conservative amino acid change located in the Alstrom syndrome repeat region (IPR040972) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249080 control chromosomes (gnomAD v2.1). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4598A>G in individuals affected with Alstrom Syndrome with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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