ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.785C>T (p.Thr262Ile)

gnomAD frequency: 0.00058  dbSNP: rs147940796
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536672 SCV000631733 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 262 of the PLOD1 protein (p.Thr262Ile). This variant is present in population databases (rs147940796, 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: 459828). 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 C15"). 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 RCV000536672 SCV001159705 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2018-10-24 criteria provided, single submitter clinical testing The PLOD1 c.785C>T; p.Thr262Ile variant (rs147940796), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 459828). This variant is found in the African population with an overall allele frequency of 0.15% (37/24018 alleles) in the Genome Aggregation Database. The threonine at codon 262 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Thr262Ile variant is uncertain at this time.
GeneDx RCV001796098 SCV002032655 uncertain significance not provided 2021-12-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#459828; Landrum et al., 2016)
Ambry Genetics RCV003159775 SCV003871591 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-02-03 criteria provided, single submitter clinical testing The p.T262I variant (also known as c.785C>T), located in coding exon 8 of the PLOD1 gene, results from a C to T substitution at nucleotide position 785. The threonine at codon 262 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. 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.

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