Submissions for variant NM_001277115.2(DNAH11):c.6506C>T (p.Ser2169Leu)

gnomAD frequency: 0.00016  dbSNP: rs373946181

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000814773	SCV000955198	pathogenic	Primary ciliary dyskinesia	2025-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2169 of the DNAH11 protein (p.Ser2169Leu). This variant is present in population databases (rs373946181, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of primary ciliary dyskinesia (PMID: 29467202; internal data). ClinVar contains an entry for this variant (Variation ID: 658037). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNAH11 protein function. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000814773	SCV002655564	likely pathogenic	Primary ciliary dyskinesia	2022-06-14	criteria provided, single submitter	clinical testing	The p.S2169L variant (also known as c.6506C>T), located in coding exon 39 of the DNAH11 gene, results from a C to T substitution at nucleotide position 6506. The serine at codon 2169 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been detected in the homozygous state, and in conjunction with a pathogenic DNAH11 mutation, in multiple unrelated individuals with primary ciliary dyskinesia (Shoemark A et al. Eur Respir J, 2018 02;51:; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005036198	SCV005666837	likely pathogenic	Primary ciliary dyskinesia 7	2024-04-15	criteria provided, single submitter	clinical testing
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill	RCV000814773	SCV001431638	uncertain significance	Primary ciliary dyskinesia	2018-12-13	flagged submission	clinical testing