Laboratory Medicine Online

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