TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21359	64300;64301;64302	chr2:178587136;178587135;178587134	chr2:179451863;179451862;179451861
N2AB	19718	59377;59378;59379	chr2:178587136;178587135;178587134	chr2:179451863;179451862;179451861
N2A	18791	56596;56597;56598	chr2:178587136;178587135;178587134	chr2:179451863;179451862;179451861
N2B	12294	37105;37106;37107	chr2:178587136;178587135;178587134	chr2:179451863;179451862;179451861
Novex-1	12419	37480;37481;37482	chr2:178587136;178587135;178587134	chr2:179451863;179451862;179451861
Novex-2	12486	37681;37682;37683	chr2:178587136;178587135;178587134	chr2:179451863;179451862;179451861
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-42
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.4721
• 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
L/V	None	None	0.802	N	0.724	0.083	0.293147016451	gnomAD-4.0.0	1.59242E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86107E-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
L/A	0.2267	likely_benign	0.1734	benign	-1.039	Destabilizing	0.963	D	0.77	deleterious	None	None	None	None	N
L/C	0.5387	ambiguous	0.4436	ambiguous	-0.789	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/D	0.8256	likely_pathogenic	0.7488	pathogenic	0.022	Stabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
L/E	0.4719	ambiguous	0.3712	ambiguous	-0.023	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
L/F	0.1801	likely_benign	0.1447	benign	-0.777	Destabilizing	0.986	D	0.742	deleterious	N	0.487654463	None	None	N
L/G	0.6087	likely_pathogenic	0.5064	ambiguous	-1.276	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
L/H	0.2572	likely_benign	0.1909	benign	-0.427	Destabilizing	0.999	D	0.813	deleterious	N	0.471934535	None	None	N
L/I	0.1063	likely_benign	0.0964	benign	-0.508	Destabilizing	0.125	N	0.429	neutral	N	0.433435976	None	None	N
L/K	0.2068	likely_benign	0.1557	benign	-0.5	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
L/M	0.1167	likely_benign	0.114	benign	-0.46	Destabilizing	0.995	D	0.703	prob.delet.	None	None	None	None	N
L/N	0.4582	ambiguous	0.3772	ambiguous	-0.317	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
L/P	0.297	likely_benign	0.2224	benign	-0.651	Destabilizing	0.998	D	0.819	deleterious	N	0.478428995	None	None	N
L/Q	0.1446	likely_benign	0.1091	benign	-0.498	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
L/R	0.1715	likely_benign	0.1183	benign	0.035	Stabilizing	0.998	D	0.826	deleterious	N	0.463046807	None	None	N
L/S	0.34	ambiguous	0.2703	benign	-0.953	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
L/T	0.1857	likely_benign	0.1479	benign	-0.879	Destabilizing	0.989	D	0.705	prob.delet.	None	None	None	None	N
L/V	0.0953	likely_benign	0.0847	benign	-0.651	Destabilizing	0.802	D	0.724	deleterious	N	0.454368608	None	None	N
L/W	0.3511	ambiguous	0.2683	benign	-0.763	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
L/Y	0.4142	ambiguous	0.3373	benign	-0.531	Destabilizing	0.998	D	0.759	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.