Submissions for variant NM_000302.4(PLOD1):c.77-3358C>T

gnomAD frequency: 0.00153  dbSNP: rs534978828

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001732231	SCV001984655	likely benign	Ehlers-Danlos syndrome, kyphoscoliotic type 1	2020-06-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001732231	SCV003799291	uncertain significance	Ehlers-Danlos syndrome, kyphoscoliotic type 1	2023-11-22	criteria provided, single submitter	clinical testing	The PLOD1 c.173C>T; p.Ser58Phe variant (rs534978828), also known as c.77-3358C>T in transcript NM_000302.4, is not reported in the medical literature or gene-specific databases, to our knowledge. This variant is found in the non-Finnish European population with an overall allele frequency of 0.24% (296/120954 alleles) in the Genome Aggregation Database. The serine at codon 58 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.004). This variant occurs in a weakly conserved exon that is expressed at low levels in the Genotype-Tissue Expression (GTEx) database (see link), suggesting it may not occur in physiologically relevant transcript. However, given the lack of clinical and functional data, the significance of the p.Ser58Phe variant is uncertain at this time. References: Link to PLOD1 in GTEx Portal: https://www.gtexportal.org/home/gene/PLOD1
PreventionGenetics, part of Exact Sciences	RCV003968491	SCV004779546	likely benign	PLOD1-related disorder	2022-01-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702293	SCV001932291	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702293	SCV001972327	likely benign	not provided		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV001732231	SCV002074945	not provided	Ehlers-Danlos syndrome, kyphoscoliotic type 1		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 04-23-2020 by Lab or GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.