TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31970	96133;96134;96135	chr2:178544321;178544320;178544319	chr2:179409048;179409047;179409046
N2AB	30329	91210;91211;91212	chr2:178544321;178544320;178544319	chr2:179409048;179409047;179409046
N2A	29402	88429;88430;88431	chr2:178544321;178544320;178544319	chr2:179409048;179409047;179409046
N2B	22905	68938;68939;68940	chr2:178544321;178544320;178544319	chr2:179409048;179409047;179409046
Novex-1	23030	69313;69314;69315	chr2:178544321;178544320;178544319	chr2:179409048;179409047;179409046
Novex-2	23097	69514;69515;69516	chr2:178544321;178544320;178544319	chr2:179409048;179409047;179409046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-121
• Domain position: 62
• Structural Position: 91
• Q(SASA): 0.1325
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
F/L	None	None	0.978	N	0.498	0.405	0.317084106153	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
F/A	0.8346	likely_pathogenic	0.8469	pathogenic	-2.45	Highly Destabilizing	0.992	D	0.514	neutral	None	None	None	None	I
F/C	0.3584	ambiguous	0.3943	ambiguous	-1.956	Destabilizing	1.0	D	0.691	prob.neutral	N	0.473768019	None	None	I
F/D	0.9519	likely_pathogenic	0.9544	pathogenic	-2.529	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	I
F/E	0.9576	likely_pathogenic	0.9601	pathogenic	-2.35	Highly Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
F/G	0.9218	likely_pathogenic	0.9264	pathogenic	-2.849	Highly Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
F/H	0.6785	likely_pathogenic	0.7002	pathogenic	-1.322	Destabilizing	0.995	D	0.61	neutral	None	None	None	None	I
F/I	0.4335	ambiguous	0.4528	ambiguous	-1.177	Destabilizing	0.997	D	0.471	neutral	N	0.501357265	None	None	I
F/K	0.9413	likely_pathogenic	0.943	pathogenic	-2.288	Highly Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	I
F/L	0.8993	likely_pathogenic	0.9142	pathogenic	-1.177	Destabilizing	0.978	D	0.498	neutral	N	0.474381308	None	None	I
F/M	0.6398	likely_pathogenic	0.6671	pathogenic	-1.005	Destabilizing	1.0	D	0.519	neutral	None	None	None	None	I
F/N	0.8658	likely_pathogenic	0.8829	pathogenic	-2.745	Highly Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	I
F/P	0.9993	likely_pathogenic	0.9993	pathogenic	-1.607	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
F/Q	0.9123	likely_pathogenic	0.92	pathogenic	-2.652	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
F/R	0.9082	likely_pathogenic	0.9104	pathogenic	-1.819	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	I
F/S	0.7967	likely_pathogenic	0.8181	pathogenic	-3.383	Highly Destabilizing	0.997	D	0.605	neutral	N	0.486728016	None	None	I
F/T	0.8538	likely_pathogenic	0.8697	pathogenic	-3.087	Highly Destabilizing	0.998	D	0.629	neutral	None	None	None	None	I
F/V	0.4453	ambiguous	0.4756	ambiguous	-1.607	Destabilizing	0.978	D	0.46	neutral	N	0.493502999	None	None	I
F/W	0.5482	ambiguous	0.5619	ambiguous	-0.389	Destabilizing	0.999	D	0.507	neutral	None	None	None	None	I
F/Y	0.1186	likely_benign	0.1146	benign	-0.725	Destabilizing	0.198	N	0.252	neutral	N	0.43638028	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.