ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.2099A>G (p.His700Arg)

gnomAD frequency: 0.00002  dbSNP: rs773756799
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000801914 SCV000941715 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-06-06 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 700 of the PLOD1 protein (p.His700Arg). This variant is present in population databases (rs773756799, gnomAD 0.002%). 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: 647407). 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: "Probably 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 RCV000801914 SCV001160433 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2019-04-13 criteria provided, single submitter clinical testing The PLOD1 c.2099A>G; p.His700Arg variant (rs773756799), to our knowledge, has not been reported in the medical literature or gene specific databases. This variant is found in the general population with an allele frequency in non-Finnish Europeans of 0.0018% (2/113,558 alleles) in the Genome Aggregation Database. The histidine at codon 700 is highly conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, based on the available information, the clinical significance of this variant is uncertain.
Ambry Genetics RCV002422741 SCV002724508 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-11-20 criteria provided, single submitter clinical testing The p.H700R variant (also known as c.2099A>G), located in coding exon 19 of the PLOD1 gene, results from an A to G substitution at nucleotide position 2099. The histidine at codon 700 is replaced by arginine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV003884735 SCV004700139 likely pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing PLOD1: PM1, PM2, PM3:Supporting, PP3

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