TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15629	47110;47111;47112	chr2:178618665;178618664;178618663	chr2:179483392;179483391;179483390
N2AB	13988	42187;42188;42189	chr2:178618665;178618664;178618663	chr2:179483392;179483391;179483390
N2A	13061	39406;39407;39408	chr2:178618665;178618664;178618663	chr2:179483392;179483391;179483390
N2B	6564	19915;19916;19917	chr2:178618665;178618664;178618663	chr2:179483392;179483391;179483390
Novex-1	6689	20290;20291;20292	chr2:178618665;178618664;178618663	chr2:179483392;179483391;179483390
Novex-2	6756	20491;20492;20493	chr2:178618665;178618664;178618663	chr2:179483392;179483391;179483390
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-108
• Domain position: 62
• Structural Position: 146
• Q(SASA): 0.7173
• Predicted PPI site: I

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
K/R	rs774914362	0.303	0.505	N	0.383	0.105	0.252681307341	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-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
K/A	0.1759	likely_benign	0.2727	benign	0.067	Stabilizing	0.404	N	0.411	neutral	None	None	None	None	I
K/C	0.6932	likely_pathogenic	0.8188	pathogenic	-0.37	Destabilizing	0.973	D	0.481	neutral	None	None	None	None	I
K/D	0.4043	ambiguous	0.561	ambiguous	-0.11	Destabilizing	0.404	N	0.418	neutral	None	None	None	None	I
K/E	0.1231	likely_benign	0.1982	benign	-0.097	Destabilizing	0.505	D	0.413	neutral	N	0.445614473	None	None	I
K/F	0.6489	likely_pathogenic	0.7873	pathogenic	-0.154	Destabilizing	0.906	D	0.463	neutral	None	None	None	None	I
K/G	0.3421	ambiguous	0.4917	ambiguous	-0.111	Destabilizing	0.404	N	0.437	neutral	None	None	None	None	I
K/H	0.3022	likely_benign	0.4121	ambiguous	-0.239	Destabilizing	0.973	D	0.411	neutral	None	None	None	None	I
K/I	0.2201	likely_benign	0.3258	benign	0.458	Stabilizing	0.642	D	0.473	neutral	N	0.447929989	None	None	I
K/L	0.2184	likely_benign	0.3513	ambiguous	0.458	Stabilizing	0.404	N	0.424	neutral	None	None	None	None	I
K/M	0.1716	likely_benign	0.2733	benign	0.007	Stabilizing	0.973	D	0.415	neutral	None	None	None	None	I
K/N	0.2716	likely_benign	0.4016	ambiguous	0.064	Stabilizing	0.003	N	0.252	neutral	N	0.452522379	None	None	I
K/P	0.2976	likely_benign	0.3867	ambiguous	0.354	Stabilizing	0.004	N	0.263	neutral	None	None	None	None	I
K/Q	0.125	likely_benign	0.1781	benign	-0.044	Destabilizing	0.782	D	0.388	neutral	N	0.450438219	None	None	I
K/R	0.0848	likely_benign	0.0977	benign	-0.069	Destabilizing	0.505	D	0.383	neutral	N	0.440816852	None	None	I
K/S	0.2687	likely_benign	0.4071	ambiguous	-0.329	Destabilizing	0.404	N	0.377	neutral	None	None	None	None	I
K/T	0.1223	likely_benign	0.1935	benign	-0.178	Destabilizing	0.003	N	0.261	neutral	N	0.44727312	None	None	I
K/V	0.2152	likely_benign	0.3148	benign	0.354	Stabilizing	0.404	N	0.422	neutral	None	None	None	None	I
K/W	0.7145	likely_pathogenic	0.8211	pathogenic	-0.243	Destabilizing	0.991	D	0.579	neutral	None	None	None	None	I
K/Y	0.5136	ambiguous	0.6636	pathogenic	0.113	Stabilizing	0.906	D	0.455	neutral	None	None	None	None	I

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.