ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.1730G>C (p.Arg577Thr) (rs397515541)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000629262 SCV000750197 pathogenic Primary ciliary dyskinesia 2019-11-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 577 of the DNAH5 protein (p.Arg577Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant also falls at the last nucleotide of exon 13 of the DNAH5 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs397515541, ExAC 0.008%). This variant has been observed with a pathogenic variant in DNAH5 in individuals with clinical features of primary ciliary dyskinesia (Invitae). It has also been reported as a single heterozygous variant in an individual with primary ciliary dyskinesia (PMID: 16627867). ClinVar contains an entry for this variant (Variation ID: 65637). Experimental studies have shown that this missense change results in skipping of exon 13 in RNA from an affected individual (PMID: 16627867). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000055850 SCV000782553 pathogenic Ciliary dyskinesia, primary, 3 2016-12-29 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000055850 SCV001315571 uncertain significance Ciliary dyskinesia, primary, 3 2017-09-01 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneReviews RCV000055850 SCV000086846 pathologic Ciliary dyskinesia, primary, 3 2011-09-15 no assertion criteria provided curation Converted during submission to Pathogenic.

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