TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22976	69151;69152;69153	chr2:178577409;178577408;178577407	chr2:179442136;179442135;179442134
N2AB	21335	64228;64229;64230	chr2:178577409;178577408;178577407	chr2:179442136;179442135;179442134
N2A	20408	61447;61448;61449	chr2:178577409;178577408;178577407	chr2:179442136;179442135;179442134
N2B	13911	41956;41957;41958	chr2:178577409;178577408;178577407	chr2:179442136;179442135;179442134
Novex-1	14036	42331;42332;42333	chr2:178577409;178577408;178577407	chr2:179442136;179442135;179442134
Novex-2	14103	42532;42533;42534	chr2:178577409;178577408;178577407	chr2:179442136;179442135;179442134
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-128
• Domain position: 27
• Structural Position: 43
• Q(SASA): 0.5551
• 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
L/F	None	None	0.884	N	0.422	0.258	0.411401001288	gnomAD-4.0.0	1.59354E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86074E-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
L/A	0.1532	likely_benign	0.1467	benign	-0.98	Destabilizing	0.373	N	0.369	neutral	None	None	None	None	I
L/C	0.4524	ambiguous	0.4544	ambiguous	-0.57	Destabilizing	0.996	D	0.454	neutral	None	None	None	None	I
L/D	0.5719	likely_pathogenic	0.581	pathogenic	-0.643	Destabilizing	0.953	D	0.514	neutral	None	None	None	None	I
L/E	0.2825	likely_benign	0.2846	benign	-0.712	Destabilizing	0.91	D	0.49	neutral	None	None	None	None	I
L/F	0.1424	likely_benign	0.1438	benign	-0.816	Destabilizing	0.884	D	0.422	neutral	N	0.482996083	None	None	I
L/G	0.4698	ambiguous	0.4862	ambiguous	-1.197	Destabilizing	0.742	D	0.483	neutral	None	None	None	None	I
L/H	0.203	likely_benign	0.207	benign	-0.494	Destabilizing	0.994	D	0.507	neutral	D	0.5261895	None	None	I
L/I	0.0889	likely_benign	0.0871	benign	-0.507	Destabilizing	0.521	D	0.356	neutral	N	0.455252121	None	None	I
L/K	0.2345	likely_benign	0.2336	benign	-0.72	Destabilizing	0.91	D	0.481	neutral	None	None	None	None	I
L/M	0.1107	likely_benign	0.1037	benign	-0.436	Destabilizing	0.953	D	0.435	neutral	None	None	None	None	I
L/N	0.2886	likely_benign	0.298	benign	-0.443	Destabilizing	0.953	D	0.522	neutral	None	None	None	None	I
L/P	0.1025	likely_benign	0.0991	benign	-0.632	Destabilizing	0.003	N	0.275	neutral	N	0.391816718	None	None	I
L/Q	0.1331	likely_benign	0.1283	benign	-0.675	Destabilizing	0.953	D	0.518	neutral	None	None	None	None	I
L/R	0.202	likely_benign	0.1991	benign	-0.108	Destabilizing	0.939	D	0.523	neutral	N	0.448632793	None	None	I
L/S	0.1806	likely_benign	0.1867	benign	-0.879	Destabilizing	0.742	D	0.463	neutral	None	None	None	None	I
L/T	0.1613	likely_benign	0.1566	benign	-0.845	Destabilizing	0.742	D	0.375	neutral	None	None	None	None	I
L/V	0.0896	likely_benign	0.085	benign	-0.632	Destabilizing	0.007	N	0.125	neutral	N	0.42600665	None	None	I
L/W	0.2849	likely_benign	0.3045	benign	-0.86	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	I
L/Y	0.2849	likely_benign	0.2879	benign	-0.64	Destabilizing	0.953	D	0.434	neutral	None	None	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.