Submissions for variant NM_000527.5(LDLR):c.779_782del (p.Asp260fs)

dbSNP: rs1600713742

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001009001	SCV001168810	likely pathogenic	not provided	2018-08-20	criteria provided, single submitter	clinical testing	Although the c.779_782delACTG likely pathogenic variant in the LDLR gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon aspartic acid 260, changing it to an alanine, and creating a premature stop codon at position 4 of the new reading frame, denoted p.Asp260AlafsX4. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the LDLR gene have been reported in Human Gene Mutation Database in association with FH (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.779_782delACTG variant has not been observed in large population cohorts (Lek et al., 2016).
Ambry Genetics	RCV002409335	SCV002674717	pathogenic	Cardiovascular phenotype	2018-01-11	criteria provided, single submitter	clinical testing	The c.779_782delACTG pathogenic mutation, located in coding exon 5 of the LDLR gene, results from a deletion of 4 nucleotides at nucleotide positions 779 to 782, causing a translational frameshift with a predicted alternate stop codon (p.D260Afs*4). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.