ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.2416A>G (p.Thr806Ala) (rs772260271)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665170 SCV000789242 uncertain significance Alstrom syndrome 2017-01-19 criteria provided, single submitter clinical testing
Invitae RCV000665170 SCV000824918 uncertain significance Alstrom syndrome 2018-03-22 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 806 of the ALMS1 protein (p.Thr806Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs772260271, ExAC 0.07%). This variant has not been reported in the literature in individuals with ALMS1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000735886 SCV000864110 uncertain significance not specified 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The ALMS1 c.2410A>G (p.Thr804Ala, alternative name c.2416A>G) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 28/276508 control chromosomes at a frequency of 0.0001013, which does not exceed the estimated maximal expected allele frequency of a pathogenic ALMS1 variant (0.0022361). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS).

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