ClinVar Miner

Submissions for variant NM_001369.2(DNAH5):c.10021C>G (p.Leu3341Val) (rs751746139)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000546641 SCV000624192 uncertain significance Primary ciliary dyskinesia 2017-04-17 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 3341 of the DNAH5 protein (p.Leu3341Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs751746139, ExAC 0.003%) but has not been reported in the literature in individuals with a DNAH5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735389 SCV000854544 uncertain significance Clinodactyly of the 5th finger; Anomalous origin of coronary artery from the pulmonary artery; Cough criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001155679 SCV001317129 uncertain significance Ciliary dyskinesia, primary, 3 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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