Submissions for variant NM_000302.4(PLOD1):c.2008C>T (p.Arg670Ter)

gnomAD frequency: 0.00003  dbSNP: rs121913554

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000015440	SCV001410212	pathogenic	Ehlers-Danlos syndrome, kyphoscoliotic type 1	2023-09-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg670*) in the PLOD1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acid(s) of the PLOD1 protein. This variant is present in population databases (rs121913554, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of Ehlers-Danlos syndrome, kyphoscoliotic form (PMID: 10874315, 32381727). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 14373). This variant disrupts a region of the PLOD1 protein in which other variant(s) (p.Gly678Arg) have been determined to be pathogenic (PMID: 21699693, 25637337). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV003311659	SCV004009733	likely pathogenic	not provided	2023-04-01	criteria provided, single submitter	clinical testing	PLOD1: PVS1:Strong, PM2, PM3
OMIM	RCV000015440	SCV000035705	pathogenic	Ehlers-Danlos syndrome, kyphoscoliotic type 1	2017-12-21	no assertion criteria provided	literature only