ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4204A>G (p.Thr1402Ala) (rs199649563)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229674 SCV000290085 uncertain significance Alstrom syndrome 2016-01-01 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1403 of the ALMS1 protein (p.Thr1403Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs199649563, ExAC 0.07%) but has not been reported in the literature in individuals with a ALMS1-related disease. The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. However, algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000480638 SCV000573176 uncertain significance not provided 2021-07-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Nilou-Genome Lab RCV000229674 SCV001712335 uncertain significance Alstrom syndrome 2021-05-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV000229674 SCV001453454 likely benign Alstrom syndrome 2020-01-01 no assertion criteria provided clinical testing

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