ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.307G>A (p.Asp103Asn)

gnomAD frequency: 0.00003  dbSNP: rs774590964
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497885 SCV000590116 uncertain significance not provided 2017-05-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PLOD1 gene. The D103N variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D103N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV000526172 SCV000631721 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 103 of the PLOD1 protein (p.Asp103Asn). This variant is present in population databases (rs774590964, gnomAD 0.005%). 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: 432397). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002314855 SCV000739543 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-01-30 criteria provided, single submitter clinical testing The p.D103N variant (also known as c.307G>A), located in coding exon 4 of the PLOD1 gene, results from a G to A substitution at nucleotide position 307. The aspartic acid at codon 103 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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 RCV000526172 SCV002776766 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2021-07-11 criteria provided, single submitter clinical testing

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