ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.11216G>A (p.Arg3739Gln) (rs200378498)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669481 SCV000794238 uncertain significance Alstrom syndrome 2017-09-20 criteria provided, single submitter clinical testing
Invitae RCV000669481 SCV000940821 uncertain significance Alstrom syndrome 2018-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 3739 of the ALMS1 protein (p.Arg3739Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200378498, ExAC 0.05%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 553938). 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.
Integrated Genetics/Laboratory Corporation of America RCV001175432 SCV001338982 uncertain significance not specified 2020-03-23 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.11210G>A (p.Arg3737Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 248248 control chromosomes. 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.11210G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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