TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35323	106192;106193;106194	chr2:178530648;178530647;178530646	chr2:179395375;179395374;179395373
N2AB	33682	101269;101270;101271	chr2:178530648;178530647;178530646	chr2:179395375;179395374;179395373
N2A	32755	98488;98489;98490	chr2:178530648;178530647;178530646	chr2:179395375;179395374;179395373
N2B	26258	78997;78998;78999	chr2:178530648;178530647;178530646	chr2:179395375;179395374;179395373
Novex-1	26383	79372;79373;79374	chr2:178530648;178530647;178530646	chr2:179395375;179395374;179395373
Novex-2	26450	79573;79574;79575	chr2:178530648;178530647;178530646	chr2:179395375;179395374;179395373
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-165
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.3398
• Predicted PPI site: N

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
G/S	rs372749780	-0.613	0.916	N	0.363	0.265	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
G/S	rs372749780	-0.613	0.916	N	0.363	0.265	None	gnomAD-4.0.0	1.36827E-06	None	None	None	None	N	None	2.98704E-05	0	None	0	0	None	0	0	0	0	1.6564E-05

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
G/A	0.4249	ambiguous	0.3835	ambiguous	-0.309	Destabilizing	0.984	D	0.449	neutral	N	0.495320892	None	None	N
G/C	0.4998	ambiguous	0.4633	ambiguous	-0.889	Destabilizing	1.0	D	0.736	prob.delet.	N	0.460784677	None	None	N
G/D	0.2694	likely_benign	0.2553	benign	-0.5	Destabilizing	0.998	D	0.705	prob.neutral	N	0.491590484	None	None	N
G/E	0.3059	likely_benign	0.2747	benign	-0.635	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
G/F	0.9115	likely_pathogenic	0.8891	pathogenic	-0.891	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
G/H	0.572	likely_pathogenic	0.5258	ambiguous	-0.481	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
G/I	0.8301	likely_pathogenic	0.778	pathogenic	-0.359	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
G/K	0.4725	ambiguous	0.418	ambiguous	-0.872	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
G/L	0.8561	likely_pathogenic	0.8218	pathogenic	-0.359	Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
G/M	0.8462	likely_pathogenic	0.8053	pathogenic	-0.544	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
G/N	0.3505	ambiguous	0.3175	benign	-0.555	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
G/P	0.9905	likely_pathogenic	0.9895	pathogenic	-0.308	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
G/Q	0.3798	ambiguous	0.3405	ambiguous	-0.786	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
G/R	0.3352	likely_benign	0.2966	benign	-0.439	Destabilizing	0.999	D	0.714	prob.delet.	N	0.486673612	None	None	N
G/S	0.1682	likely_benign	0.1585	benign	-0.731	Destabilizing	0.916	D	0.363	neutral	N	0.463516474	None	None	N
G/T	0.5535	ambiguous	0.4927	ambiguous	-0.787	Destabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	N
G/V	0.7544	likely_pathogenic	0.7015	pathogenic	-0.308	Destabilizing	0.896	D	0.47	neutral	N	0.514439105	None	None	N
G/W	0.7509	likely_pathogenic	0.7167	pathogenic	-1.077	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
G/Y	0.7949	likely_pathogenic	0.7412	pathogenic	-0.721	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N

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.