TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7336	22231;22232;22233	chr2:178722893;178722892;178722891	chr2:179587620;179587619;179587618
N2AB	7019	21280;21281;21282	chr2:178722893;178722892;178722891	chr2:179587620;179587619;179587618
N2A	6092	18499;18500;18501	chr2:178722893;178722892;178722891	chr2:179587620;179587619;179587618
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-58
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.7042
• Predicted PPI site: I

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
V/A	rs1323509026	-0.335	0.012	N	0.095	0.167	0.176091768786	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	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
V/A	0.0882	likely_benign	0.1036	benign	-0.973	Destabilizing	0.012	N	0.095	neutral	N	0.407377164	None	None	I
V/C	0.7734	likely_pathogenic	0.7858	pathogenic	-0.682	Destabilizing	0.996	D	0.305	neutral	None	None	None	None	I
V/D	0.3116	likely_benign	0.3765	ambiguous	-0.64	Destabilizing	0.939	D	0.379	neutral	N	0.476874535	None	None	I
V/E	0.2016	likely_benign	0.2498	benign	-0.721	Destabilizing	0.742	D	0.388	neutral	None	None	None	None	I
V/F	0.1427	likely_benign	0.1629	benign	-0.986	Destabilizing	0.007	N	0.232	neutral	N	0.453858916	None	None	I
V/G	0.1856	likely_benign	0.2373	benign	-1.186	Destabilizing	0.521	D	0.431	neutral	N	0.462506197	None	None	I
V/H	0.5144	ambiguous	0.5785	pathogenic	-0.708	Destabilizing	0.996	D	0.338	neutral	None	None	None	None	I
V/I	0.065	likely_benign	0.0646	benign	-0.531	Destabilizing	0.007	N	0.234	neutral	N	0.43004338	None	None	I
V/K	0.2805	likely_benign	0.3339	benign	-0.8	Destabilizing	0.59	D	0.407	neutral	None	None	None	None	I
V/L	0.1406	likely_benign	0.1511	benign	-0.531	Destabilizing	0.134	N	0.317	neutral	N	0.453592243	None	None	I
V/M	0.1105	likely_benign	0.1244	benign	-0.388	Destabilizing	0.91	D	0.29	neutral	None	None	None	None	I
V/N	0.2298	likely_benign	0.2776	benign	-0.479	Destabilizing	0.953	D	0.375	neutral	None	None	None	None	I
V/P	0.3113	likely_benign	0.3487	ambiguous	-0.642	Destabilizing	0.953	D	0.361	neutral	None	None	None	None	I
V/Q	0.2639	likely_benign	0.3099	benign	-0.725	Destabilizing	0.91	D	0.351	neutral	None	None	None	None	I
V/R	0.2493	likely_benign	0.3	benign	-0.226	Destabilizing	0.02	N	0.372	neutral	None	None	None	None	I
V/S	0.1416	likely_benign	0.1723	benign	-0.919	Destabilizing	0.59	D	0.416	neutral	None	None	None	None	I
V/T	0.1154	likely_benign	0.1287	benign	-0.895	Destabilizing	0.742	D	0.339	neutral	None	None	None	None	I
V/W	0.7419	likely_pathogenic	0.7885	pathogenic	-1.08	Destabilizing	0.996	D	0.358	neutral	None	None	None	None	I
V/Y	0.5135	ambiguous	0.5654	pathogenic	-0.798	Destabilizing	0.835	D	0.345	neutral	None	None	None	None	I

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.