ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.842G>A (p.Gly281Glu)

gnomAD frequency: 0.00003  dbSNP: rs1056398577
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315166 SCV000739558 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-08-24 criteria provided, single submitter clinical testing The p.G281E variant (also known as c.842G>A), located in coding exon 8 of the PLOD1 gene, results from a G to A substitution at nucleotide position 842. The glycine at codon 281 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and glutamic acid is the reference amino acid in other 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.
Invitae RCV000802332 SCV000942157 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-06-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 281 of the PLOD1 protein (p.Gly281Glu). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 520122). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.

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