TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24845	74758;74759;74760	chr2:178571599;178571598;178571597	chr2:179436326;179436325;179436324
N2AB	23204	69835;69836;69837	chr2:178571599;178571598;178571597	chr2:179436326;179436325;179436324
N2A	22277	67054;67055;67056	chr2:178571599;178571598;178571597	chr2:179436326;179436325;179436324
N2B	15780	47563;47564;47565	chr2:178571599;178571598;178571597	chr2:179436326;179436325;179436324
Novex-1	15905	47938;47939;47940	chr2:178571599;178571598;178571597	chr2:179436326;179436325;179436324
Novex-2	15972	48139;48140;48141	chr2:178571599;178571598;178571597	chr2:179436326;179436325;179436324
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-68
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1452
• 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
I/L	rs1214451388	-1.452	0.889	N	0.412	0.133	0.542100083394	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	6.49E-05	0	None	0	0	None	0	None	0	3.59E-05	0
I/L	rs1214451388	-1.452	0.889	N	0.412	0.133	0.542100083394	gnomAD-4.0.0	1.50576E-05	None	None	None	None	N	None	2.98954E-05	0	None	0	0	None	0	0	1.6193E-05	0	4.97216E-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
I/A	0.7512	likely_pathogenic	0.7341	pathogenic	-2.86	Highly Destabilizing	0.992	D	0.62	neutral	None	None	None	None	N
I/C	0.8741	likely_pathogenic	0.8553	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
I/D	0.9851	likely_pathogenic	0.9813	pathogenic	-3.362	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
I/E	0.9487	likely_pathogenic	0.9382	pathogenic	-3.164	Highly Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
I/F	0.4951	ambiguous	0.4303	ambiguous	-1.734	Destabilizing	0.998	D	0.67	neutral	N	0.479825028	None	None	N
I/G	0.9743	likely_pathogenic	0.9693	pathogenic	-3.357	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
I/H	0.8941	likely_pathogenic	0.8713	pathogenic	-2.715	Highly Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
I/K	0.8929	likely_pathogenic	0.8721	pathogenic	-2.262	Highly Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
I/L	0.3337	likely_benign	0.2844	benign	-1.417	Destabilizing	0.889	D	0.412	neutral	N	0.468682532	None	None	N
I/M	0.2625	likely_benign	0.2046	benign	-1.386	Destabilizing	0.998	D	0.677	prob.neutral	N	0.495398068	None	None	N
I/N	0.8403	likely_pathogenic	0.8144	pathogenic	-2.579	Highly Destabilizing	0.999	D	0.769	deleterious	N	0.470808899	None	None	N
I/P	0.9949	likely_pathogenic	0.9952	pathogenic	-1.881	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
I/Q	0.8981	likely_pathogenic	0.8757	pathogenic	-2.497	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
I/R	0.818	likely_pathogenic	0.7883	pathogenic	-1.823	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
I/S	0.7232	likely_pathogenic	0.701	pathogenic	-3.213	Highly Destabilizing	0.998	D	0.635	neutral	N	0.479251915	None	None	N
I/T	0.3282	likely_benign	0.3254	benign	-2.889	Highly Destabilizing	0.989	D	0.634	neutral	N	0.494601865	None	None	N
I/V	0.074	likely_benign	0.0732	benign	-1.881	Destabilizing	0.333	N	0.205	neutral	N	0.48532902	None	None	N
I/W	0.9509	likely_pathogenic	0.932	pathogenic	-2.125	Highly Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
I/Y	0.8561	likely_pathogenic	0.8242	pathogenic	-1.921	Destabilizing	1.0	D	0.658	neutral	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.