ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.109G>A (p.Glu37Lys)

gnomAD frequency: 0.00004  dbSNP: rs369263247
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532117 SCV000631684 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 37 of the PLOD1 protein (p.Glu37Lys). This variant is present in population databases (rs369263247, gnomAD 0.2%). 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: 459803). 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: "Tolerated"; 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000532117 SCV000885983 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2019-08-12 criteria provided, single submitter clinical testing
GeneDx RCV001527341 SCV001738312 uncertain significance not provided 2020-05-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002448653 SCV002734590 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-01-30 criteria provided, single submitter clinical testing The c.109G>A (p.E37K) alteration is located in exon 2 (coding exon 2) of the PLOD1 gene. This alteration results from a G to A substitution at nucleotide position 109, causing the glutamic acid (E) at amino acid position 37 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000532117 SCV002786167 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2021-10-07 criteria provided, single submitter clinical testing
Refractive Surgery Department, Bright Eye Hospital RCV003324532 SCV004030248 likely pathogenic Keratoconus 2023-08-04 no assertion criteria provided clinical testing In this study, a heterozygous PLOD1 mutation c.109G>A was detected in family 1, which is located in exon 2 and causes a p.Glu37Lys amino acid change. The conformational alteration of the protein caused by this variant may disturb the crosslinking of corneal fibrils. In addition, PPI network showed the interaction between PLOD1 and COL1A1 or PLOD1 and COL5A1. Therefore, misfolding and/or aggregate formation of PLOD1 likely cause the development of KC by disturbing corneal crosslinking. To date, this is the first report to identify a PLOD1 mutation in a family with KC.

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