TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9507	28744;28745;28746	chr2:178709800;178709799;178709798	chr2:179574527;179574526;179574525
N2AB	9190	27793;27794;27795	chr2:178709800;178709799;178709798	chr2:179574527;179574526;179574525
N2A	8263	25012;25013;25014	chr2:178709800;178709799;178709798	chr2:179574527;179574526;179574525
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-81
• Domain position: 15
• Structural Position: 23
• Q(SASA): 0.7761
• 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
E/Q	None	None	0.984	None	0.449	0.304	0.28058544554	gnomAD-4.0.0	2.05297E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.6984E-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
E/A	0.1235	likely_benign	0.1165	benign	-0.553	Destabilizing	0.103	N	0.29	neutral	None	None	None	None	I
E/C	0.9087	likely_pathogenic	0.8909	pathogenic	0.027	Stabilizing	0.999	D	0.641	neutral	None	None	None	None	I
E/D	0.3116	likely_benign	0.2522	benign	-0.597	Destabilizing	0.026	N	0.283	neutral	None	None	None	None	I
E/F	0.8323	likely_pathogenic	0.7893	pathogenic	-0.55	Destabilizing	0.988	D	0.613	neutral	None	None	None	None	I
E/G	0.256	likely_benign	0.2065	benign	-0.786	Destabilizing	0.896	D	0.545	neutral	None	None	None	None	I
E/H	0.6541	likely_pathogenic	0.5891	pathogenic	-0.619	Destabilizing	0.999	D	0.383	neutral	None	None	None	None	I
E/I	0.3625	ambiguous	0.3237	benign	0.038	Stabilizing	0.952	D	0.532	neutral	None	None	None	None	I
E/K	0.1447	likely_benign	0.1223	benign	0.076	Stabilizing	0.896	D	0.49	neutral	None	None	None	None	I
E/L	0.4465	ambiguous	0.3984	ambiguous	0.038	Stabilizing	0.851	D	0.563	neutral	None	None	None	None	I
E/M	0.4867	ambiguous	0.4492	ambiguous	0.381	Stabilizing	0.997	D	0.571	neutral	None	None	None	None	I
E/N	0.436	ambiguous	0.3628	ambiguous	-0.157	Destabilizing	0.952	D	0.421	neutral	None	None	None	None	I
E/P	0.6823	likely_pathogenic	0.6246	pathogenic	-0.138	Destabilizing	0.988	D	0.479	neutral	None	None	None	None	I
E/Q	0.1706	likely_benign	0.1515	benign	-0.133	Destabilizing	0.984	D	0.449	neutral	None	None	None	None	I
E/R	0.2774	likely_benign	0.2333	benign	0.196	Stabilizing	0.988	D	0.415	neutral	None	None	None	None	I
E/S	0.2632	likely_benign	0.2225	benign	-0.358	Destabilizing	0.851	D	0.453	neutral	None	None	None	None	I
E/T	0.2918	likely_benign	0.247	benign	-0.176	Destabilizing	0.919	D	0.525	neutral	None	None	None	None	I
E/V	0.206	likely_benign	0.1871	benign	-0.138	Destabilizing	0.211	N	0.374	neutral	None	None	None	None	I
E/W	0.9471	likely_pathogenic	0.9264	pathogenic	-0.428	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
E/Y	0.7523	likely_pathogenic	0.6945	pathogenic	-0.316	Destabilizing	0.996	D	0.579	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.