ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.1427A>G (p.Lys476Arg)

gnomAD frequency: 0.00025  dbSNP: rs576907642
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594652 SCV000703958 uncertain significance not provided 2017-01-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000764960 SCV000896135 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000764960 SCV001505579 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-05-13 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 476 of the PLOD1 protein (p.Lys476Arg). This variant is present in population databases (rs576907642, gnomAD 0.1%). 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: 498773). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002279376 SCV002566010 uncertain significance Ehlers-Danlos syndrome 2019-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002395525 SCV002698682 likely benign Familial thoracic aortic aneurysm and aortic dissection 2024-11-27 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003330814 SCV004039250 uncertain significance not specified 2023-08-24 criteria provided, single submitter clinical testing
GeneDx RCV000594652 SCV005437585 uncertain significance not provided 2024-06-16 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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