TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16820	50683;50684;50685	chr2:178611851;178611850;178611849	chr2:179476578;179476577;179476576
N2AB	15179	45760;45761;45762	chr2:178611851;178611850;178611849	chr2:179476578;179476577;179476576
N2A	14252	42979;42980;42981	chr2:178611851;178611850;178611849	chr2:179476578;179476577;179476576
N2B	7755	23488;23489;23490	chr2:178611851;178611850;178611849	chr2:179476578;179476577;179476576
Novex-1	7880	23863;23864;23865	chr2:178611851;178611850;178611849	chr2:179476578;179476577;179476576
Novex-2	7947	24064;24065;24066	chr2:178611851;178611850;178611849	chr2:179476578;179476577;179476576
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-10
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1779
• 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
T/K	None	None	0.993	N	0.719	0.403	0.514811571519	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
T/A	0.2096	likely_benign	0.1746	benign	-0.851	Destabilizing	0.977	D	0.436	neutral	N	0.48965272	None	None	N
T/C	0.7043	likely_pathogenic	0.6128	pathogenic	-0.602	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
T/D	0.7759	likely_pathogenic	0.773	pathogenic	0.05	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
T/E	0.6702	likely_pathogenic	0.6704	pathogenic	0.057	Stabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
T/F	0.7346	likely_pathogenic	0.6994	pathogenic	-0.885	Destabilizing	0.995	D	0.738	prob.delet.	None	None	None	None	N
T/G	0.4773	ambiguous	0.4489	ambiguous	-1.108	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
T/H	0.6597	likely_pathogenic	0.6069	pathogenic	-1.309	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/I	0.7173	likely_pathogenic	0.6884	pathogenic	-0.259	Destabilizing	0.987	D	0.709	prob.delet.	D	0.525222026	None	None	N
T/K	0.6153	likely_pathogenic	0.5877	pathogenic	-0.62	Destabilizing	0.993	D	0.719	prob.delet.	N	0.494084507	None	None	N
T/L	0.3624	ambiguous	0.3356	benign	-0.259	Destabilizing	0.906	D	0.47	neutral	None	None	None	None	N
T/M	0.2196	likely_benign	0.1939	benign	-0.089	Destabilizing	0.921	D	0.407	neutral	None	None	None	None	N
T/N	0.3138	likely_benign	0.3091	benign	-0.57	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
T/P	0.875	likely_pathogenic	0.8543	pathogenic	-0.424	Destabilizing	0.999	D	0.723	prob.delet.	D	0.675380282	None	None	N
T/Q	0.4936	ambiguous	0.4875	ambiguous	-0.726	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
T/R	0.5715	likely_pathogenic	0.5338	ambiguous	-0.409	Destabilizing	0.997	D	0.721	prob.delet.	N	0.488419691	None	None	N
T/S	0.1769	likely_benign	0.171	benign	-0.919	Destabilizing	0.989	D	0.495	neutral	N	0.493377405	None	None	N
T/V	0.4778	ambiguous	0.4436	ambiguous	-0.424	Destabilizing	0.966	D	0.465	neutral	None	None	None	None	N
T/W	0.906	likely_pathogenic	0.8958	pathogenic	-0.778	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
T/Y	0.7521	likely_pathogenic	0.7149	pathogenic	-0.55	Destabilizing	0.998	D	0.743	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.