TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24824	74695;74696;74697	chr2:178571662;178571661;178571660	chr2:179436389;179436388;179436387
N2AB	23183	69772;69773;69774	chr2:178571662;178571661;178571660	chr2:179436389;179436388;179436387
N2A	22256	66991;66992;66993	chr2:178571662;178571661;178571660	chr2:179436389;179436388;179436387
N2B	15759	47500;47501;47502	chr2:178571662;178571661;178571660	chr2:179436389;179436388;179436387
Novex-1	15884	47875;47876;47877	chr2:178571662;178571661;178571660	chr2:179436389;179436388;179436387
Novex-2	15951	48076;48077;48078	chr2:178571662;178571661;178571660	chr2:179436389;179436388;179436387
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-68
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.4762
• 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
D/Y	None	None	1.0	N	0.729	0.461	0.724662712665	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.5848	likely_pathogenic	0.5435	ambiguous	-0.429	Destabilizing	0.999	D	0.729	prob.delet.	N	0.484170348	None	None	N
D/C	0.9166	likely_pathogenic	0.9131	pathogenic	0.131	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
D/E	0.2944	likely_benign	0.2964	benign	-0.593	Destabilizing	0.767	D	0.308	neutral	N	0.463897742	None	None	N
D/F	0.929	likely_pathogenic	0.9179	pathogenic	-0.704	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
D/G	0.5832	likely_pathogenic	0.552	ambiguous	-0.651	Destabilizing	0.998	D	0.696	prob.neutral	N	0.473129985	None	None	N
D/H	0.7864	likely_pathogenic	0.7543	pathogenic	-0.98	Destabilizing	1.0	D	0.675	prob.neutral	D	0.522868688	None	None	N
D/I	0.8636	likely_pathogenic	0.8574	pathogenic	0.114	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/K	0.8724	likely_pathogenic	0.859	pathogenic	0.086	Stabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
D/L	0.8429	likely_pathogenic	0.8299	pathogenic	0.114	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
D/M	0.9204	likely_pathogenic	0.9068	pathogenic	0.604	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
D/N	0.2492	likely_benign	0.2119	benign	-0.136	Destabilizing	0.999	D	0.651	neutral	N	0.482288715	None	None	N
D/P	0.9893	likely_pathogenic	0.9883	pathogenic	-0.045	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
D/Q	0.7624	likely_pathogenic	0.726	pathogenic	-0.119	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
D/R	0.8985	likely_pathogenic	0.8815	pathogenic	None	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
D/S	0.3371	likely_benign	0.2897	benign	-0.278	Destabilizing	0.997	D	0.623	neutral	None	None	None	None	N
D/T	0.5156	ambiguous	0.4653	ambiguous	-0.103	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/V	0.6884	likely_pathogenic	0.6788	pathogenic	-0.045	Destabilizing	0.999	D	0.731	prob.delet.	N	0.504173934	None	None	N
D/W	0.9885	likely_pathogenic	0.9872	pathogenic	-0.674	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
D/Y	0.6947	likely_pathogenic	0.6733	pathogenic	-0.494	Destabilizing	1.0	D	0.729	prob.delet.	N	0.503920445	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.