ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.323C>T (p.Ser108Leu)

dbSNP: rs549517196
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315163 SCV000739554 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-05-19 criteria provided, single submitter clinical testing The p.S108L variant (also known as c.323C>T), located in coding exon 4 of the PLOD1 gene, results from a C to T substitution at nucleotide position 323. The serine at codon 108 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001771835 SCV002003079 uncertain significance not provided 2020-02-11 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001803898 SCV002050127 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2021-08-20 criteria provided, single submitter clinical testing The PLOD1 c.323C>T; p.Ser108Leu variant (rs549517196), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 520119). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 108 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.327). Due to limited information, the clinical significance of the p.Ser108Leu variant is uncertain at this time.
Invitae RCV001803898 SCV003294291 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-06-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 108 of the PLOD1 protein (p.Ser108Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 520119). 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 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.

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