TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35508	106747;106748;106749	chr2:178529969;178529968;178529967	chr2:179394696;179394695;179394694
N2AB	33867	101824;101825;101826	chr2:178529969;178529968;178529967	chr2:179394696;179394695;179394694
N2A	32940	99043;99044;99045	chr2:178529969;178529968;178529967	chr2:179394696;179394695;179394694
N2B	26443	79552;79553;79554	chr2:178529969;178529968;178529967	chr2:179394696;179394695;179394694
Novex-1	26568	79927;79928;79929	chr2:178529969;178529968;178529967	chr2:179394696;179394695;179394694
Novex-2	26635	80128;80129;80130	chr2:178529969;178529968;178529967	chr2:179394696;179394695;179394694
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: Ig-166
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.2589
• 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/S	None	None	0.785	D	0.531	0.179	0.326345978581	gnomAD-4.0.0	6.94625E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0347E-07	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
T/A	0.1123	likely_benign	0.1134	benign	-0.938	Destabilizing	0.426	N	0.561	neutral	D	0.529307163	None	None	N
T/C	0.6523	likely_pathogenic	0.6657	pathogenic	-0.64	Destabilizing	0.995	D	0.638	neutral	None	None	None	None	N
T/D	0.3751	ambiguous	0.3792	ambiguous	-0.381	Destabilizing	0.981	D	0.589	neutral	None	None	None	None	N
T/E	0.3059	likely_benign	0.3066	benign	-0.37	Destabilizing	0.981	D	0.593	neutral	None	None	None	None	N
T/F	0.253	likely_benign	0.2475	benign	-0.973	Destabilizing	0.893	D	0.702	prob.neutral	None	None	None	None	N
T/G	0.3517	ambiguous	0.3759	ambiguous	-1.203	Destabilizing	0.944	D	0.627	neutral	None	None	None	None	N
T/H	0.2824	likely_benign	0.2819	benign	-1.472	Destabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	N
T/I	0.1651	likely_benign	0.1566	benign	-0.319	Destabilizing	0.006	N	0.414	neutral	N	0.485442975	None	None	N
T/K	0.2338	likely_benign	0.2265	benign	-0.769	Destabilizing	0.928	D	0.593	neutral	D	0.52459199	None	None	N
T/L	0.1265	likely_benign	0.1303	benign	-0.319	Destabilizing	0.145	N	0.545	neutral	None	None	None	None	N
T/M	0.107	likely_benign	0.1135	benign	0.001	Stabilizing	0.893	D	0.669	neutral	None	None	None	None	N
T/N	0.1342	likely_benign	0.1337	benign	-0.731	Destabilizing	0.981	D	0.563	neutral	None	None	None	None	N
T/P	0.477	ambiguous	0.4943	ambiguous	-0.494	Destabilizing	0.975	D	0.665	neutral	D	0.538136352	None	None	N
T/Q	0.2413	likely_benign	0.2417	benign	-0.929	Destabilizing	0.981	D	0.673	neutral	None	None	None	None	N
T/R	0.1859	likely_benign	0.1809	benign	-0.541	Destabilizing	0.928	D	0.669	neutral	D	0.527653724	None	None	N
T/S	0.1331	likely_benign	0.1395	benign	-1.039	Destabilizing	0.785	D	0.531	neutral	D	0.525440138	None	None	N
T/V	0.1663	likely_benign	0.1583	benign	-0.494	Destabilizing	0.145	N	0.489	neutral	None	None	None	None	N
T/W	0.6174	likely_pathogenic	0.6284	pathogenic	-0.868	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
T/Y	0.3204	likely_benign	0.3213	benign	-0.642	Destabilizing	0.944	D	0.715	prob.delet.	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.