ClinVar Miner

Submissions for variant NM_003114.5(SPAG1):c.2515A>T (p.Met839Leu)

gnomAD frequency: 0.00017  dbSNP: rs142674953
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000466776 SCV000551910 uncertain significance Primary ciliary dyskinesia 28 2024-05-08 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 839 of the SPAG1 protein (p.Met839Leu). This variant is present in population databases (rs142674953, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 411000). 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 SPAG1 protein function with a negative predictive value of 80%. 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 RCV002429534 SCV002744295 uncertain significance Primary ciliary dyskinesia 2024-06-18 criteria provided, single submitter clinical testing The p.M839L variant (also known as c.2515A>T), located in coding exon 17 of the SPAG1 gene, results from an A to T substitution at nucleotide position 2515. The methionine at codon 839 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000466776 SCV002817067 uncertain significance Primary ciliary dyskinesia 28 2021-10-19 criteria provided, single submitter clinical testing

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