TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18440	55543;55544;55545	chr2:178601772;178601771;178601770	chr2:179466499;179466498;179466497
N2AB	16799	50620;50621;50622	chr2:178601772;178601771;178601770	chr2:179466499;179466498;179466497
N2A	15872	47839;47840;47841	chr2:178601772;178601771;178601770	chr2:179466499;179466498;179466497
N2B	9375	28348;28349;28350	chr2:178601772;178601771;178601770	chr2:179466499;179466498;179466497
Novex-1	9500	28723;28724;28725	chr2:178601772;178601771;178601770	chr2:179466499;179466498;179466497
Novex-2	9567	28924;28925;28926	chr2:178601772;178601771;178601770	chr2:179466499;179466498;179466497
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-115
• Domain position: 59
• Structural Position: 134
• Q(SASA): 0.4888
• 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
N/K	rs911563094	None	0.101	N	0.261	0.076	0.159798565429	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/K	rs911563094	None	0.101	N	0.261	0.076	0.159798565429	gnomAD-4.0.0	2.4939E-06	None	None	None	None	N	None	1.3464E-05	0	None	0	0	None	0	0	2.54973E-06	0	0
N/S	rs747117847	-0.682	0.047	N	0.209	0.103	0.184867976434	gnomAD-2.1.1	4.2E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.17E-06	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
N/A	0.2164	likely_benign	0.356	ambiguous	-0.416	Destabilizing	0.061	N	0.434	neutral	None	None	None	None	N
N/C	0.3079	likely_benign	0.4404	ambiguous	0.321	Stabilizing	0.983	D	0.505	neutral	None	None	None	None	N
N/D	0.1276	likely_benign	0.2109	benign	0.125	Stabilizing	0.101	N	0.282	neutral	N	0.420350114	None	None	N
N/E	0.339	likely_benign	0.5141	ambiguous	0.113	Stabilizing	0.001	N	0.102	neutral	None	None	None	None	N
N/F	0.4575	ambiguous	0.5618	ambiguous	-0.622	Destabilizing	0.836	D	0.535	neutral	None	None	None	None	N
N/G	0.2227	likely_benign	0.3356	benign	-0.631	Destabilizing	0.001	N	0.107	neutral	None	None	None	None	N
N/H	0.1233	likely_benign	0.1699	benign	-0.605	Destabilizing	0.794	D	0.407	neutral	N	0.485652386	None	None	N
N/I	0.2258	likely_benign	0.3216	benign	0.072	Stabilizing	0.351	N	0.517	neutral	N	0.478014338	None	None	N
N/K	0.2375	likely_benign	0.4034	ambiguous	0.009	Stabilizing	0.101	N	0.261	neutral	N	0.448902152	None	None	N
N/L	0.2668	likely_benign	0.379	ambiguous	0.072	Stabilizing	0.129	N	0.502	neutral	None	None	None	None	N
N/M	0.2853	likely_benign	0.3952	ambiguous	0.415	Stabilizing	0.94	D	0.498	neutral	None	None	None	None	N
N/P	0.6953	likely_pathogenic	0.8453	pathogenic	-0.063	Destabilizing	0.593	D	0.512	neutral	None	None	None	None	N
N/Q	0.2935	likely_benign	0.4364	ambiguous	-0.429	Destabilizing	0.264	N	0.29	neutral	None	None	None	None	N
N/R	0.3259	likely_benign	0.4993	ambiguous	0.036	Stabilizing	0.418	N	0.258	neutral	None	None	None	None	N
N/S	0.0983	likely_benign	0.1438	benign	-0.262	Destabilizing	0.047	N	0.209	neutral	N	0.442610898	None	None	N
N/T	0.1119	likely_benign	0.17	benign	-0.118	Destabilizing	0.001	N	0.122	neutral	N	0.38681633	None	None	N
N/V	0.2503	likely_benign	0.3643	ambiguous	-0.063	Destabilizing	0.129	N	0.498	neutral	None	None	None	None	N
N/W	0.7098	likely_pathogenic	0.8226	pathogenic	-0.546	Destabilizing	0.983	D	0.513	neutral	None	None	None	None	N
N/Y	0.147	likely_benign	0.1742	benign	-0.31	Destabilizing	0.921	D	0.51	neutral	N	0.450635736	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.