TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24760	74503;74504;74505	chr2:178571854;178571853;178571852	chr2:179436581;179436580;179436579
N2AB	23119	69580;69581;69582	chr2:178571854;178571853;178571852	chr2:179436581;179436580;179436579
N2A	22192	66799;66800;66801	chr2:178571854;178571853;178571852	chr2:179436581;179436580;179436579
N2B	15695	47308;47309;47310	chr2:178571854;178571853;178571852	chr2:179436581;179436580;179436579
Novex-1	15820	47683;47684;47685	chr2:178571854;178571853;178571852	chr2:179436581;179436580;179436579
Novex-2	15887	47884;47885;47886	chr2:178571854;178571853;178571852	chr2:179436581;179436580;179436579
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-133
• Domain position: 45
• Structural Position: 109
• Q(SASA): 0.7893
• 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/S	rs762222770	None	0.822	N	0.363	0.17	0.0954503805726	gnomAD-4.0.0	4.77514E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57795E-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
T/A	0.1528	likely_benign	0.1554	benign	-0.143	Destabilizing	0.656	D	0.383	neutral	N	0.471156497	None	None	N
T/C	0.8157	likely_pathogenic	0.8202	pathogenic	-0.285	Destabilizing	0.998	D	0.448	neutral	None	None	None	None	N
T/D	0.7593	likely_pathogenic	0.7532	pathogenic	0.018	Stabilizing	0.978	D	0.391	neutral	None	None	None	None	N
T/E	0.6618	likely_pathogenic	0.6467	pathogenic	-0.073	Destabilizing	0.956	D	0.383	neutral	None	None	None	None	N
T/F	0.6654	likely_pathogenic	0.663	pathogenic	-0.795	Destabilizing	0.978	D	0.501	neutral	None	None	None	None	N
T/G	0.4312	ambiguous	0.4314	ambiguous	-0.211	Destabilizing	0.956	D	0.398	neutral	None	None	None	None	N
T/H	0.6278	likely_pathogenic	0.6237	pathogenic	-0.398	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
T/I	0.5027	ambiguous	0.4919	ambiguous	-0.089	Destabilizing	0.125	N	0.329	neutral	N	0.468022698	None	None	N
T/K	0.5336	ambiguous	0.5388	ambiguous	-0.261	Destabilizing	0.956	D	0.388	neutral	None	None	None	None	N
T/L	0.192	likely_benign	0.1976	benign	-0.089	Destabilizing	0.754	D	0.39	neutral	None	None	None	None	N
T/M	0.1526	likely_benign	0.1561	benign	-0.093	Destabilizing	0.994	D	0.399	neutral	None	None	None	None	N
T/N	0.3258	likely_benign	0.3369	benign	-0.031	Destabilizing	0.97	D	0.377	neutral	N	0.46576932	None	None	N
T/P	0.2775	likely_benign	0.2843	benign	-0.082	Destabilizing	0.014	N	0.329	neutral	N	0.443431178	None	None	N
T/Q	0.4625	ambiguous	0.4683	ambiguous	-0.244	Destabilizing	0.978	D	0.396	neutral	None	None	None	None	N
T/R	0.5148	ambiguous	0.5114	ambiguous	0.025	Stabilizing	0.978	D	0.387	neutral	None	None	None	None	N
T/S	0.1765	likely_benign	0.1846	benign	-0.191	Destabilizing	0.822	D	0.363	neutral	N	0.411222759	None	None	N
T/V	0.3078	likely_benign	0.3063	benign	-0.082	Destabilizing	0.754	D	0.383	neutral	None	None	None	None	N
T/W	0.9014	likely_pathogenic	0.9036	pathogenic	-0.883	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	N
T/Y	0.7047	likely_pathogenic	0.7093	pathogenic	-0.558	Destabilizing	0.993	D	0.496	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.