ClinVar Miner

Submissions for variant NM_015681.5(B9D1):c.434C>T (p.Thr145Ile) (rs765607415)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540095 SCV000634616 uncertain significance Joubert syndrome; Meckel-Gruber syndrome 2017-08-29 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 145 of the B9D1 protein (p.Thr145Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs765607415, ExAC 0.003%). This variant has been reported in an individual affected with Joubert syndrome (PMID: 26477546). It is also known as a nonsense variant, c.493C>T (p.Gln165*), in the final exon of an alternate B9D1 transcript (NM_001243473.1). This would be expected to delete the last 93 amino acids of the protein translated from the alternate transcript. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.

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