TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5008	15247;15248;15249	chr2:178734902;178734901;178734900	chr2:179599629;179599628;179599627
N2AB	4691	14296;14297;14298	chr2:178734902;178734901;178734900	chr2:179599629;179599628;179599627
N2A	3764	11515;11516;11517	chr2:178734902;178734901;178734900	chr2:179599629;179599628;179599627
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-33
• Domain position: 28
• Structural Position: 41
• Q(SASA): 0.4335
• 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
S/L	None	None	1.0	N	0.695	0.425	0.813890695137	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	1.26695E-04	0	None	0	0	None	0	0	0	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
S/A	0.2059	likely_benign	0.1714	benign	-0.085	Destabilizing	0.997	D	0.562	neutral	D	0.529509179	None	None	I
S/C	0.3833	ambiguous	0.3204	benign	-0.387	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
S/D	0.7769	likely_pathogenic	0.7389	pathogenic	0.117	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
S/E	0.8519	likely_pathogenic	0.8112	pathogenic	0.022	Stabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
S/F	0.324	likely_benign	0.2469	benign	-0.789	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
S/G	0.3219	likely_benign	0.3525	ambiguous	-0.155	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	I
S/H	0.6295	likely_pathogenic	0.5564	ambiguous	-0.473	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
S/I	0.4018	ambiguous	0.3028	benign	-0.036	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
S/K	0.9297	likely_pathogenic	0.8985	pathogenic	-0.371	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
S/L	0.1934	likely_benign	0.16	benign	-0.036	Destabilizing	1.0	D	0.695	prob.neutral	N	0.512068058	None	None	I
S/M	0.3492	ambiguous	0.3176	benign	-0.155	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
S/N	0.3677	ambiguous	0.3102	benign	-0.146	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
S/P	0.9028	likely_pathogenic	0.9218	pathogenic	-0.026	Destabilizing	1.0	D	0.741	deleterious	D	0.672907569	None	None	I
S/Q	0.8057	likely_pathogenic	0.7577	pathogenic	-0.333	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
S/R	0.9112	likely_pathogenic	0.8696	pathogenic	-0.135	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
S/T	0.1133	likely_benign	0.126	benign	-0.226	Destabilizing	0.999	D	0.551	neutral	N	0.503766431	None	None	I
S/V	0.4062	ambiguous	0.3238	benign	-0.026	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
S/W	0.5636	ambiguous	0.5031	ambiguous	-0.9	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
S/Y	0.3164	likely_benign	0.2546	benign	-0.562	Destabilizing	1.0	D	0.809	deleterious	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.