ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.5177T>C (p.Leu1726Pro) (rs138890576)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000408603 SCV000484425 likely pathogenic Ciliary dyskinesia, primary, 3 2014-11-20 criteria provided, single submitter clinical testing This substitution is predicted to create a change of a leucine to a proline at amino acid position 1726, NP_001360.1(DNAH5): p.(Leu1726Pro). The leucine at this position is highly conserved and is located in the dynein heavy chain domain. Grantham assessment is likely deleterious based on conservation and amino acid properties. In-silico software predicts this variant to be disease-causing. This variant is present in population databases at a low frequency (EVS MAF EA:0.0116, AA:0.00, All:0.0077), consistent with carrier rate for a rare autosomal recessive condition. It was identified in trans with a previously published pathogenic mutation in DNAH5, c.10815delT, p.(Pro3606Hisfs*23) in this patient.
Invitae RCV000525295 SCV000624265 pathogenic Primary ciliary dyskinesia 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1726 of the DNAH5 protein (p.Leu1726Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs138890576, ExAC 0.001%). This variant has been observed in several individuals affected with primary ciliary dyskinesia (PMID: 26228299, 29453417, Invitae) including at least one individual in which this variant was observed on the opposite chromosome (in trans) from another pathogenic variant (PMID: 26938784). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. 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: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV000525295 SCV001457366 pathogenic Primary ciliary dyskinesia 2020-09-16 no assertion criteria provided clinical testing

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