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Table. 1.

Table. 1.

Re-classification of VUS of the LDLR gene

Exon Nucleotide substitution Amino acid substitution Clinvar ID ClinVar status ClinVar classification* Previous classification ClinGen guideline evidence Re-classification PopMax KRGDB REVEL score MES score
3 c.268G >T p.(Asp90Tyr) 251106 2-star LPV VUS PM5_Strong, PM2, PP3 LPV N/A N/A 0.958 N/A
4 c.694G>T p.(Ala232Ser) 689347 1-star VUS VUS PM1, PM2, PS3_Supporting§, PP3 LPV N/A N/A 0.373 0.177
5 c.769C >T p.(Arg257Trp) 251446 1-star LPV (3); VUS (6); PV (1) VUS PM5, BS3§ VUS 0.100% N/A 0.648 N/A
5 c.781T>A p.(Cys261Ser) N/A N/A N/A VUS PM1, PM2, PP3 VUS N/A N/A 0.963 N/A
Intron 5 c.817+14A> G p.(?) 889873 1-star VUS VUS BP4 VUS 0.080% 0.117% N/A 1.000
Intron 5 c.818-15C>G p.(?) 919422 1-star LBV VUS None VUS 0.098% 0.117% N/A 0.970
6 c.939C >T p.(Cys313= ) N/A N/A N/A VUS None VUS 0.022% 0.029% N/A 0.853
8 c.1105G>A p.(Val369Met) 183107 1-star VUS VUS PM2 VUS 0.002% N/A 0.643 N/A
Intron 9 c.1358+10G >A p.(?) 431526 1-star VUS VUS PM2, BP4 VUS 0.016% 0.088% N/A 1.000
Intron 10 c.1587-11C>T p.(?) 548078 star LBV (1); VUS (1) VUS PM2, BP4 VUS 0.010% 0.059% N/A 1.080
11 c.1640T >C p.(Leu547Pro) 251949 1-star VUS (1); LPV (2) VUS PM2, PS4_Supporting, PP3, PP4 VUS N/A N/A 0.883 N/A
12 c.1765G>A p.(Asp589Asn) 252022 star VUS VUS PM5, PS4_Supporting, BP4 VUS 0.110% N/A 0.325 N/A
15 c.2191G >A p.(Val731Ile) N/A N/A N/A VUS PM2, BP4 VUS N/A N/A 0.115 N/A
4 c.344G>A p.(Arg115His) 225402 star LBV (1); VUS (3); LPV (2); PV (1) LBV BS1, PM1 VUS 0.230% 0.466% 0.684 N/A
9 c.1228A >G p.(Arg410Gly) 430781 1-star LPV LPV PM2, PM5, PS4_Supporting VUS N/A N/A 0.699 N/A
10 c.1571_1573del p.(Val524del) 841257 star PV LPV PM2, PM4 VUS N/A N/A N/A N/A

*When ClinVar classification had conflicting interpretations of pathogenicity, the number of interpretions was expressed in parenthesis (Last accessed on July 2021). gnomAD subpopulation with the highest allele frequency; Ratio of variant MES score/wild-type MES score; §Functional evidence of variants c.694G>T and c.769C>T are made according to Rodríguez-Jiménez et al. [20] and Etxebarria et al. [22], respectively.

Abbreviations: VUS, variant of uncertain significance; LBV, likely benign variant; LPV, likely pathogenic variant; KRGDB, Korean Reference Genome Database; MES, MaxEntScan; PV, pathogenic variant; N/A, not applicable.

Lab Med Online 2022;12:116~121 https://doi.org/10.47429/lmo.2022.12.2.116
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