Submissions for variant NM_000302.4(PLOD1):c.-9_2del (p.Met1fs)

dbSNP: rs747037908

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482810	SCV000572215	uncertain significance	not provided	2024-09-19	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Alters the Kozak sequence, which plays a major role in the initiation of translation
Ambry Genetics	RCV002376884	SCV002686286	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-05-08	criteria provided, single submitter	clinical testing	The c.-9_2del11 variant (also known as p.M1?), located in the 5' untranslated region (5'UTR) and coding exon 1 of the PLOD1 gene, results from a deletion of 11 nucleotides between positions -9 and 2. This deletion interrupts the native ATG initiation codon; however, the remaining realigned nucleotides recreate an ATG initiation codon at the same position and is predicted to maintain the normal reading frame. However, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002481525	SCV002783644	uncertain significance	Ehlers-Danlos syndrome, kyphoscoliotic type 1	2022-05-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586735	SCV005076082	uncertain significance	not specified	2024-10-18	criteria provided, single submitter	clinical testing	Variant summary: PLOD1 c.-9_2del11 is a small deletion located in the 5' untranslated region and the first coding exon. It encompasses the first two nucleotides of the start codon. However, the remaining upstream nucleotides restore the sequence of the start codon, likely maintaining the original reading frame. This indicates the variant is less likely to be associated with disease, however functional studies have not been performed. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.-9_2del11 in individuals affected with Ehlers-Danlos Syndrome Type VI and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 422689). Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000482810	SCV005436135	uncertain significance	not provided	2024-10-01	criteria provided, single submitter	clinical testing	PLOD1: PM2, BP4