ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.1511A>G (p.His504Arg)

gnomAD frequency: 0.00001  dbSNP: rs555034048
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634752 SCV000756095 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 504 of the PLOD1 protein (p.His504Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. 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 arginine 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.
Ambry Genetics RCV002388026 SCV002709779 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-08-22 criteria provided, single submitter clinical testing The p.H504R variant (also known as c.1511A>G), located in coding exon 14 of the PLOD1 gene, results from an A to G substitution at nucleotide position 1511. The histidine at codon 504 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
PreventionGenetics, part of Exact Sciences RCV003403458 SCV004112042 uncertain significance PLOD1-related condition 2023-08-17 criteria provided, single submitter clinical testing The PLOD1 c.1511A>G variant is predicted to result in the amino acid substitution p.His504Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-12025577-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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