. 2024 Oct 25;45(1):33. doi: 10.1007/s10875-024-01821-7

Table 2.

Predicted and observed levels of mutated proteins

Disease	Causative gene	Mutated allele	Mutation type	Pathogenicity determined by Mutation effect predictor^a	NMD probability^b	Predicted structural stability^c	Observed protein loss
FHL type 3	UNC13D	c.1240C > T, p.Arg414Cys	Missense mutation	Deleterious (aggregated score, 0.856)		3.28	Yes
		c.1255delC, p.Leu419Serfs*23	Frameshift		NMD		Yes
		c.1596 + 1G > C	Splicing anomaly				Yes
		c.118-308C > T	Transcriptional dysregulation		Predicted benign		Yes
		c.754-1G > C	Splicing anomaly		Exon skip 105 bp		Yes
		c.1849-1G > C	Splicing anomaly		Exon skip 144 bp		Yes
		c.1545-2A > G	Splicing anomaly		Exon skip 54 bp		Yes
FHL type 5	STXBP2	c.1430C > T, p.Pro477Leu	Missense mutation	Deleterious (aggregated score, 0.857)		4.29	Yes
FHL type 5	STXBP2	c.1197delC, p.Ala400Profs*18	Frameshift		NMD		Yes
FHL type 2	PRF1	c.658G > A, p.Gly220Ser	Missense mutation	Deleterious (aggregated score, 0.98)		14.1	No
		c.853_855delAAG, p.Lys285del	deletion	benign			No
		c.1090_1091delCT, p.Leu364Glufs*93	Frameshift		NMD escaping		No
HPS type 2	AP3B1	c.188T > A, p.Met63Lys	Missense mutation	Uncertain (aggregated score, 0.67)		5.13	No
		c.1122_1123insAG, p.Phe375Ser*11	Frameshift		NMD		Yes
		c.2546T > A, p.Leu849X	Nonsense mutation		NMD		Yes
		c.364C > T, p.Arg122X	Nonsense mutation		NMD		Reduced but detectable
		c.2810-1G > T	Splicing anomaly		Exon skip 85 bp		Reduced but detectable
CGD	CYBB	c.1031C > T, p.Ser344Phe	Missense mutation	Deleterious (aggregated score, 0.99)		12.5	Yes
		c.1528_1529delTT, p.Leu510Valfs*8	Frameshift		NMD		Yes
		c.121dupT, p.Tyr41Leufs*62	Frameshift		NMD		Yes
		c.810G > A, p.Trp270X	Nonsense mutation		NMD		Yes
		c.271C > T, p.Arg91X	Nonsense mutation		NMD		Yes
		c.252G > A, p.Ala84Ala	Splicing anomaly	Deleterious (aggregated score, 0.80)	splicing anomaly		Yes
CGD	CYBA	c.70G > A, p.Gly24Arg	Missense mutation	Deleterious (aggregated score, 0.87)		6.54	Yes
CGD	CYBA	c.7C > T, p.Gln3X	Nonsense mutation		NMD escaping		Yes
CGD	NCF1	c.75_76delGT, p.Tyr26Hisfs*26	Frameshift		NMD escaping		Reduced but detectable
WAS	WAS	c.1075C > A, p.Pro359Thr	Missense mutation	Uncertain (aggregated score, 0.54)		0.37	Yes
		c.982delC, p.Arg328Glyfs*117	Frameshift		NMD		Reduced but detectable
		c.961C > T, p.Arg321X	Nonsense mutation		NMD		Yes
		c.777 + 3_777 + 6delGAGT	Splicing anomaly				Yes
		c.132 + 1G > T	Splicing anomaly				Yes
XLA	BTK	c.95T > C, p.Leu32Ser	Missense mutation	Deleterious (aggregated score, 0.99)		5.26	Yes
		c.862C > T, p.Arg288Trp	Missense mutation	Deleterious (aggregated score, 0.88)		1.81	Yes
		c.1574G > A, p.Arg525Gln	Missense mutation	Deleterious (aggregated score, 0.88)		0.02	Yes
		c.1856C > T, p.Pro619Leu	Missense mutation	Deleterious (aggregated score, 0.87)		6.19	Yes
		c.1921C > T, p.Arg641Cys	Missense mutation	Deleterious (aggregated score, 0.88)		2.95	Yes
		c.902-904delAAG, p.Glu301del	Deletion				Yes
SCID	ADA	c.632G > A, p.Arg211His	Missense mutation	Deleterious (aggregated score, 0.99)		9.20	No
SCID	ADA	c.218 + 2T > G	Splicing anomaly				No
X-SCID	IL2RG	c.374A > G, p.Tyr125Cys	Missense mutation	Deleterious (aggregated score, 0.86)		3.36	ND
X-SCID	IL2RG	c.865C > T, p.Arg289X	Nonsense mutation		NMD escaping		ND
CHS	LYST	c.5506C > T, p.Arg1836X	Nonsense mutation		NMD		Reduced but detectable
		c.1673dupT, p.Leu558Phefs*22	Frameshift		NMD		Reduced but detectable
		c.5541_5542delAA, p.Arg1848Serfs*3	Frameshift		NMD		Reduced but detectable
		c.3393 + 1G > T	Splicing anomaly				No

FHL familial hemophagocytic lymphohistiocytosis, HPS Hermansky-Pudlak syndrome, CGD chronic granulomatous disease, WAS Wiskott-Aldrich syndrome, XLA X-linked agammaglobulinemia, X-SCID X-linked SCID, CHS Chédiak-Higashi syndrome

^aAggregated prediction score obtained using Franklin (https://franklin.genoox.com/clinical-db/home)

^bNonsense medeated decay (NMD) prediction using Variant Effect Predictor

^cProtein structure was predicted to be destabilized with a score > 1