TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2616	8071;8072;8073	chr2:178773118;178773117;178773116	chr2:179637845;179637844;179637843
N2AB	2616	8071;8072;8073	chr2:178773118;178773117;178773116	chr2:179637845;179637844;179637843
N2A	2616	8071;8072;8073	chr2:178773118;178773117;178773116	chr2:179637845;179637844;179637843
N2B	2570	7933;7934;7935	chr2:178773118;178773117;178773116	chr2:179637845;179637844;179637843
Novex-1	2570	7933;7934;7935	chr2:178773118;178773117;178773116	chr2:179637845;179637844;179637843
Novex-2	2570	7933;7934;7935	chr2:178773118;178773117;178773116	chr2:179637845;179637844;179637843
Novex-3	2616	8071;8072;8073	chr2:178773118;178773117;178773116	chr2:179637845;179637844;179637843

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-15
• Domain position: 84
• Structural Position: 175
• Q(SASA): 0.2373
• 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/A	None	None	0.309	N	0.367	0.128	0.223146558224	gnomAD-4.0.0	1.59109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85731E-06	0	0
T/I	None	None	0.015	N	0.243	0.211	0.177238962908	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	0
T/P	None	None	0.939	D	0.403	0.321	0.361958692863	gnomAD-4.0.0	1.59109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-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
T/A	0.1122	likely_benign	0.122	benign	-0.463	Destabilizing	0.309	N	0.367	neutral	N	0.479934269	None	None	N
T/C	0.4726	ambiguous	0.5055	ambiguous	-0.245	Destabilizing	0.996	D	0.397	neutral	None	None	None	None	N
T/D	0.4196	ambiguous	0.42	ambiguous	-0.044	Destabilizing	0.59	D	0.346	neutral	None	None	None	None	N
T/E	0.2543	likely_benign	0.2713	benign	-0.089	Destabilizing	0.742	D	0.345	neutral	None	None	None	None	N
T/F	0.1956	likely_benign	0.1938	benign	-0.679	Destabilizing	0.91	D	0.482	neutral	None	None	None	None	N
T/G	0.4438	ambiguous	0.4577	ambiguous	-0.667	Destabilizing	0.59	D	0.397	neutral	None	None	None	None	N
T/H	0.1994	likely_benign	0.2024	benign	-0.951	Destabilizing	0.987	D	0.462	neutral	None	None	None	None	N
T/I	0.105	likely_benign	0.1059	benign	-0.032	Destabilizing	0.015	N	0.243	neutral	N	0.453797528	None	None	N
T/K	0.1438	likely_benign	0.1455	benign	-0.592	Destabilizing	0.742	D	0.355	neutral	None	None	None	None	N
T/L	0.0854	likely_benign	0.0935	benign	-0.032	Destabilizing	0.373	N	0.381	neutral	None	None	None	None	N
T/M	0.0857	likely_benign	0.0929	benign	0.172	Stabilizing	0.91	D	0.397	neutral	None	None	None	None	N
T/N	0.1428	likely_benign	0.1437	benign	-0.347	Destabilizing	0.015	N	0.211	neutral	N	0.442501975	None	None	N
T/P	0.5863	likely_pathogenic	0.622	pathogenic	-0.144	Destabilizing	0.939	D	0.403	neutral	D	0.578824472	None	None	N
T/Q	0.1814	likely_benign	0.1964	benign	-0.559	Destabilizing	0.91	D	0.427	neutral	None	None	None	None	N
T/R	0.1166	likely_benign	0.1216	benign	-0.301	Destabilizing	0.91	D	0.405	neutral	None	None	None	None	N
T/S	0.1478	likely_benign	0.1507	benign	-0.574	Destabilizing	0.078	N	0.228	neutral	N	0.478900894	None	None	N
T/V	0.1152	likely_benign	0.1178	benign	-0.144	Destabilizing	0.009	N	0.222	neutral	None	None	None	None	N
T/W	0.5129	ambiguous	0.5273	ambiguous	-0.659	Destabilizing	0.996	D	0.567	neutral	None	None	None	None	N
T/Y	0.2641	likely_benign	0.2685	benign	-0.419	Destabilizing	0.953	D	0.478	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.