Submissions for variant NM_000527.5(LDLR):c.2233_2291del (p.Pro745fs)

dbSNP: rs1555808094

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598937	SCV000710534	likely pathogenic	not provided	2018-02-05	criteria provided, single submitter	clinical testing	The c.2233_2291del59 pathogenic variant in the LDLR gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.2233_2291del59 variant causes a frameshift starting with codon Proline 745, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 17 of the new reading frame, denoted p.Pro745SerfsX17. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2233_2291del59 variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.2233_2291del59 as a likelyl pathogenic variant.
Ambry Genetics	RCV004024879	SCV004072598	pathogenic	Cardiovascular phenotype	2023-06-23	criteria provided, single submitter	clinical testing	The c.2233_2291del59 (p.P745Sfs*17) alteration, located in exon 15 (coding exon 15) of the LDLR gene, consists of a deletion of 59 nucleotides from position 2233 to 2291, causing a translational frameshift with a predicted alternate stop codon after 17 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic.