TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2483	7672;7673;7674	chr2:178773609;178773608;178773607	chr2:179638336;179638335;179638334
N2AB	2483	7672;7673;7674	chr2:178773609;178773608;178773607	chr2:179638336;179638335;179638334
N2A	2483	7672;7673;7674	chr2:178773609;178773608;178773607	chr2:179638336;179638335;179638334
N2B	2437	7534;7535;7536	chr2:178773609;178773608;178773607	chr2:179638336;179638335;179638334
Novex-1	2437	7534;7535;7536	chr2:178773609;178773608;178773607	chr2:179638336;179638335;179638334
Novex-2	2437	7534;7535;7536	chr2:178773609;178773608;178773607	chr2:179638336;179638335;179638334
Novex-3	2483	7672;7673;7674	chr2:178773609;178773608;178773607	chr2:179638336;179638335;179638334

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-14
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.7674
• 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
E/K	None	None	0.003	N	0.148	0.251	0.255270683199	gnomAD-4.0.0	6.84109E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99318E-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
E/A	0.1297	likely_benign	0.1295	benign	-0.52	Destabilizing	0.183	N	0.339	neutral	N	0.501854428	None	None	N
E/C	0.6119	likely_pathogenic	0.6001	pathogenic	-0.315	Destabilizing	0.983	D	0.287	neutral	None	None	None	None	N
E/D	0.1038	likely_benign	0.1083	benign	-0.528	Destabilizing	0.002	N	0.195	neutral	N	0.505798843	None	None	N
E/F	0.5322	ambiguous	0.5201	ambiguous	-0.209	Destabilizing	0.836	D	0.304	neutral	None	None	None	None	N
E/G	0.1489	likely_benign	0.1484	benign	-0.753	Destabilizing	0.213	N	0.355	neutral	N	0.515339559	None	None	N
E/H	0.2515	likely_benign	0.2461	benign	0.059	Stabilizing	0.005	N	0.194	neutral	None	None	None	None	N
E/I	0.1873	likely_benign	0.184	benign	0.077	Stabilizing	0.836	D	0.317	neutral	None	None	None	None	N
E/K	0.077	likely_benign	0.0752	benign	0.029	Stabilizing	0.003	N	0.148	neutral	N	0.401745938	None	None	N
E/L	0.2502	likely_benign	0.2453	benign	0.077	Stabilizing	0.418	N	0.391	neutral	None	None	None	None	N
E/M	0.2865	likely_benign	0.28	benign	0.107	Stabilizing	0.983	D	0.277	neutral	None	None	None	None	N
E/N	0.134	likely_benign	0.1358	benign	-0.402	Destabilizing	0.002	N	0.251	neutral	None	None	None	None	N
E/P	0.8168	likely_pathogenic	0.8142	pathogenic	-0.102	Destabilizing	0.836	D	0.355	neutral	None	None	None	None	N
E/Q	0.088	likely_benign	0.0874	benign	-0.333	Destabilizing	0.007	N	0.203	neutral	N	0.443969642	None	None	N
E/R	0.1414	likely_benign	0.1364	benign	0.368	Stabilizing	0.264	N	0.289	neutral	None	None	None	None	N
E/S	0.1374	likely_benign	0.1374	benign	-0.564	Destabilizing	0.129	N	0.301	neutral	None	None	None	None	N
E/T	0.14	likely_benign	0.1396	benign	-0.371	Destabilizing	0.418	N	0.353	neutral	None	None	None	None	N
E/V	0.128	likely_benign	0.1262	benign	-0.102	Destabilizing	0.523	D	0.346	neutral	N	0.449026756	None	None	N
E/W	0.7777	likely_pathogenic	0.7716	pathogenic	None	Stabilizing	0.983	D	0.311	neutral	None	None	None	None	N
E/Y	0.3823	ambiguous	0.3766	ambiguous	0.036	Stabilizing	0.716	D	0.316	neutral	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.