Description
The p.C377S variant (also known as c.1130G>C), located in coding exon 8 of the LDLR gene, results from a G to C substitution at nucleotide position 1130. The cysteine at codon 377 is replaced by serine, an amino acid with dissimilar properties, and is located in the EGF-like B domain. This alteration has been reported in a familial hypercholesterolemia (FH) cohort (Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8). In addition, other alterations involving the same amino acid position, p.C377Y (c.1130G>A), p.C377G (c.1129T>G) and p.C377F (c.1130G>T) have been reported in individuals with FH (Ekström U et al. Eur. J. Clin. Invest. 1998;28:740-7; Romano M et al, J. Lipid Res. 2011; 52:2095-100; Wu WF et al. PLoS ONE 2014; 9:e94697). Based on internal structural assessment, this alteration results in loss of a disulfide motif in EGF domain B; alterations which affect this disulfide are well-established pathogenic alterations. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |