TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23581	70966;70967;70968	chr2:178575391;178575390;178575389	chr2:179440118;179440117;179440116
N2AB	21940	66043;66044;66045	chr2:178575391;178575390;178575389	chr2:179440118;179440117;179440116
N2A	21013	63262;63263;63264	chr2:178575391;178575390;178575389	chr2:179440118;179440117;179440116
N2B	14516	43771;43772;43773	chr2:178575391;178575390;178575389	chr2:179440118;179440117;179440116
Novex-1	14641	44146;44147;44148	chr2:178575391;178575390;178575389	chr2:179440118;179440117;179440116
Novex-2	14708	44347;44348;44349	chr2:178575391;178575390;178575389	chr2:179440118;179440117;179440116
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-59
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.7266
• 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
H/R	None	None	0.521	N	0.472	0.291	0.242244723065	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85892E-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
H/A	0.2524	likely_benign	0.3461	ambiguous	-0.22	Destabilizing	0.59	D	0.522	neutral	None	None	None	None	N
H/C	0.2343	likely_benign	0.267	benign	0.363	Stabilizing	0.996	D	0.611	neutral	None	None	None	None	N
H/D	0.389	ambiguous	0.4645	ambiguous	-0.018	Destabilizing	0.684	D	0.525	neutral	N	0.455643618	None	None	N
H/E	0.391	ambiguous	0.459	ambiguous	0.02	Stabilizing	0.59	D	0.451	neutral	None	None	None	None	N
H/F	0.355	ambiguous	0.4071	ambiguous	0.529	Stabilizing	0.984	D	0.569	neutral	None	None	None	None	N
H/G	0.4019	ambiguous	0.4828	ambiguous	-0.519	Destabilizing	0.742	D	0.521	neutral	None	None	None	None	N
H/I	0.3448	ambiguous	0.4031	ambiguous	0.557	Stabilizing	0.953	D	0.589	neutral	None	None	None	None	N
H/K	0.3788	ambiguous	0.4315	ambiguous	-0.214	Destabilizing	0.009	N	0.389	neutral	None	None	None	None	N
H/L	0.1423	likely_benign	0.1763	benign	0.557	Stabilizing	0.684	D	0.545	neutral	N	0.416202583	None	None	N
H/M	0.47	ambiguous	0.5327	ambiguous	0.417	Stabilizing	0.996	D	0.578	neutral	None	None	None	None	N
H/N	0.138	likely_benign	0.1698	benign	-0.148	Destabilizing	0.684	D	0.487	neutral	N	0.461761514	None	None	N
H/P	0.1147	likely_benign	0.1517	benign	0.322	Stabilizing	0.007	N	0.396	neutral	N	0.417298661	None	None	N
H/Q	0.2475	likely_benign	0.3038	benign	-0.035	Destabilizing	0.884	D	0.509	neutral	N	0.450544443	None	None	N
H/R	0.1651	likely_benign	0.1975	benign	-0.663	Destabilizing	0.521	D	0.472	neutral	N	0.417143945	None	None	N
H/S	0.261	likely_benign	0.3376	benign	-0.176	Destabilizing	0.742	D	0.493	neutral	None	None	None	None	N
H/T	0.2846	likely_benign	0.3622	ambiguous	-0.041	Destabilizing	0.742	D	0.555	neutral	None	None	None	None	N
H/V	0.2567	likely_benign	0.3124	benign	0.322	Stabilizing	0.91	D	0.545	neutral	None	None	None	None	N
H/W	0.5131	ambiguous	0.5312	ambiguous	0.649	Stabilizing	0.996	D	0.643	neutral	None	None	None	None	N
H/Y	0.1351	likely_benign	0.1623	benign	0.88	Stabilizing	0.979	D	0.509	neutral	N	0.48983355	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.