ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.10226G>C (p.Trp3409Ser) (rs755407407)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231062 SCV000287049 pathogenic Primary ciliary dyskinesia 2019-10-31 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with serine at codon 3409 of the DNAH5 protein (p.Trp3409Ser). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and serine. This variant is present in population databases (rs755407407, ExAC 0.001%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in individuals affected with primary ciliary dyskinesia (PMID: 16627867, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 238952). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000623930 SCV000741627 likely pathogenic Inborn genetic diseases 2014-06-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected

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