ClinVar Miner

Submissions for variant NM_003114.5(SPAG1):c.1307C>A (p.Pro436Gln)

dbSNP: rs761617724
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000690010 SCV000817686 uncertain significance Primary ciliary dyskinesia 28 2021-06-24 criteria provided, single submitter clinical testing In summary, this variant is a novel 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a SPAG1-related disease. This sequence change replaces proline with glutamine at codon 436 of the SPAG1 protein (p.Pro436Gln). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and glutamine.
Ambry Genetics RCV002386186 SCV002693554 uncertain significance Primary ciliary dyskinesia 2017-04-20 criteria provided, single submitter clinical testing The p.P436Q variant (also known as c.1307C>A), located in coding exon 10 of the SPAG1 gene, results from a C to A substitution at nucleotide position 1307. The proline at codon 436 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well 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.

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