TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27554	82885;82886;82887	chr2:178563472;178563471;178563470	chr2:179428199;179428198;179428197
N2AB	25913	77962;77963;77964	chr2:178563472;178563471;178563470	chr2:179428199;179428198;179428197
N2A	24986	75181;75182;75183	chr2:178563472;178563471;178563470	chr2:179428199;179428198;179428197
N2B	18489	55690;55691;55692	chr2:178563472;178563471;178563470	chr2:179428199;179428198;179428197
Novex-1	18614	56065;56066;56067	chr2:178563472;178563471;178563470	chr2:179428199;179428198;179428197
Novex-2	18681	56266;56267;56268	chr2:178563472;178563471;178563470	chr2:179428199;179428198;179428197
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-88
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.5631
• 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
E/K	None	None	0.012	N	0.11	0.14	0.229264304666	gnomAD-4.0.0	1.36848E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79898E-06	0	0
E/Q	None	None	0.028	N	0.228	0.089	0.158396225186	gnomAD-4.0.0	6.8424E-07	None	None	None	None	I	None	2.98793E-05	0	None	0	0	None	0	0	0	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	0.1124	likely_benign	0.1015	benign	-0.233	Destabilizing	0.472	N	0.429	neutral	N	0.49822096	None	None	I
E/C	0.6713	likely_pathogenic	0.6228	pathogenic	-0.028	Destabilizing	0.996	D	0.499	neutral	None	None	None	None	I
E/D	0.1142	likely_benign	0.1043	benign	-0.317	Destabilizing	0.472	N	0.377	neutral	N	0.508341953	None	None	I
E/F	0.5227	ambiguous	0.4904	ambiguous	-0.184	Destabilizing	0.984	D	0.467	neutral	None	None	None	None	I
E/G	0.1428	likely_benign	0.1287	benign	-0.398	Destabilizing	0.684	D	0.485	neutral	N	0.481066022	None	None	I
E/H	0.3497	ambiguous	0.3126	benign	0.192	Stabilizing	0.953	D	0.432	neutral	None	None	None	None	I
E/I	0.1781	likely_benign	0.1553	benign	0.155	Stabilizing	0.91	D	0.478	neutral	None	None	None	None	I
E/K	0.0951	likely_benign	0.0815	benign	0.445	Stabilizing	0.012	N	0.11	neutral	N	0.487081246	None	None	I
E/L	0.1882	likely_benign	0.1707	benign	0.155	Stabilizing	0.742	D	0.51	neutral	None	None	None	None	I
E/M	0.2437	likely_benign	0.2231	benign	0.142	Stabilizing	0.953	D	0.46	neutral	None	None	None	None	I
E/N	0.1951	likely_benign	0.1744	benign	0.137	Stabilizing	0.742	D	0.458	neutral	None	None	None	None	I
E/P	0.2345	likely_benign	0.2199	benign	0.045	Stabilizing	0.953	D	0.505	neutral	None	None	None	None	I
E/Q	0.1017	likely_benign	0.0908	benign	0.158	Stabilizing	0.028	N	0.228	neutral	N	0.517249438	None	None	I
E/R	0.171	likely_benign	0.148	benign	0.647	Stabilizing	0.59	D	0.407	neutral	None	None	None	None	I
E/S	0.1521	likely_benign	0.1373	benign	-0.002	Destabilizing	0.373	N	0.378	neutral	None	None	None	None	I
E/T	0.1641	likely_benign	0.1468	benign	0.136	Stabilizing	0.037	N	0.303	neutral	None	None	None	None	I
E/V	0.1173	likely_benign	0.1029	benign	0.045	Stabilizing	0.684	D	0.509	neutral	N	0.478979335	None	None	I
E/W	0.7866	likely_pathogenic	0.7601	pathogenic	-0.07	Destabilizing	0.996	D	0.573	neutral	None	None	None	None	I
E/Y	0.4317	ambiguous	0.384	ambiguous	0.058	Stabilizing	0.984	D	0.467	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.