ClinVar Miner

Submissions for variant NM_001206927.2(DNAH8):c.4111G>A (p.Glu1371Lys)

gnomAD frequency: 0.00039  dbSNP: rs149020489
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001047789 SCV001211769 uncertain significance Primary ciliary dyskinesia 2022-09-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1371 of the DNAH8 protein (p.Glu1371Lys). This variant is present in population databases (rs149020489, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 844839). 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 DNAH8 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.
GeneDx RCV002298858 SCV002588157 uncertain significance not provided 2022-04-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002553172 SCV003600820 uncertain significance Inborn genetic diseases 2022-01-19 criteria provided, single submitter clinical testing The c.4111G>A (p.E1371K) alteration is located in exon 30 (coding exon 29) of the DNAH8 gene. This alteration results from a G to A substitution at nucleotide position 4111, causing the glutamic acid (E) at amino acid position 1371 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003938416 SCV004749526 uncertain significance DNAH8-related condition 2024-01-17 criteria provided, single submitter clinical testing The DNAH8 c.4111G>A variant is predicted to result in the amino acid substitution p.Glu1371Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.12% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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