Submissions for variant NM_000302.4(PLOD1):c.303C>T (p.Ser101=)

gnomAD frequency: 0.00013  dbSNP: rs147980436

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000507622	SCV000604865	likely benign	not specified	2017-03-11	criteria provided, single submitter	clinical testing
Invitae	RCV000547593	SCV000631720	uncertain significance	Ehlers-Danlos syndrome, kyphoscoliotic type 1	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change affects codon 101 of the PLOD1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PLOD1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs147980436, gnomAD 0.03%). 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: 440168). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx	RCV000507622	SCV000726603	likely benign	not specified	2018-01-22	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV002314889	SCV000739532	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-04-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Illumina Laboratory Services, Illumina	RCV000547593	SCV001257525	uncertain significance	Ehlers-Danlos syndrome, kyphoscoliotic type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV001312061	SCV001502495	likely benign	not provided	2022-07-01	criteria provided, single submitter	clinical testing	PLOD1: BP4, BP7
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001312061	SCV001742623	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001312061	SCV001807493	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001312061	SCV001927592	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001312061	SCV001951102	likely benign	not provided		no assertion criteria provided	clinical testing