Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UNC Molecular Genetics Laboratory, |
RCV001255237 | SCV001431588 | uncertain significance | Primary ciliary dyskinesia | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001255237 | SCV002279520 | uncertain significance | Primary ciliary dyskinesia | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 3276 of the DNAH11 protein (p.Leu3276Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of primary ciliary dyskinesia (Invitae). ClinVar contains an entry for this variant (Variation ID: 977533). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNAH11 protein function. 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. |
Ambry Genetics | RCV001255237 | SCV002691117 | uncertain significance | Primary ciliary dyskinesia | 2016-08-30 | criteria provided, single submitter | clinical testing | The p.L3276V variant (also known as c.9826T>G), located in coding exon 60 of the DNAH11 gene, results from a T to G substitution at nucleotide position 9826. The leucine at codon 3276 is replaced by valine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5946 samples (11892 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. |