TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20814	62665;62666;62667	chr2:178589285;178589284;178589283	chr2:179454012;179454011;179454010
N2AB	19173	57742;57743;57744	chr2:178589285;178589284;178589283	chr2:179454012;179454011;179454010
N2A	18246	54961;54962;54963	chr2:178589285;178589284;178589283	chr2:179454012;179454011;179454010
N2B	11749	35470;35471;35472	chr2:178589285;178589284;178589283	chr2:179454012;179454011;179454010
Novex-1	11874	35845;35846;35847	chr2:178589285;178589284;178589283	chr2:179454012;179454011;179454010
Novex-2	11941	36046;36047;36048	chr2:178589285;178589284;178589283	chr2:179454012;179454011;179454010
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-122
• Domain position: 46
• Structural Position: 70
• Q(SASA): 0.5881
• 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
R/G	None	None	0.896	N	0.491	0.241	0.465464902746	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
R/A	0.2668	likely_benign	0.2917	benign	-0.059	Destabilizing	0.919	D	0.539	neutral	None	None	None	None	N
R/C	0.1778	likely_benign	0.2258	benign	-0.113	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
R/D	0.4836	ambiguous	0.5649	pathogenic	-0.132	Destabilizing	0.976	D	0.451	neutral	None	None	None	None	N
R/E	0.3191	likely_benign	0.3614	ambiguous	-0.097	Destabilizing	0.851	D	0.507	neutral	None	None	None	None	N
R/F	0.5022	ambiguous	0.559	ambiguous	-0.384	Destabilizing	0.996	D	0.582	neutral	None	None	None	None	N
R/G	0.164	likely_benign	0.188	benign	-0.207	Destabilizing	0.896	D	0.491	neutral	N	0.460735299	None	None	N
R/H	0.1086	likely_benign	0.1235	benign	-0.666	Destabilizing	0.996	D	0.477	neutral	None	None	None	None	N
R/I	0.262	likely_benign	0.2878	benign	0.288	Stabilizing	0.984	D	0.581	neutral	N	0.466026476	None	None	N
R/K	0.0876	likely_benign	0.093	benign	-0.059	Destabilizing	0.011	N	0.179	neutral	N	0.449555513	None	None	N
R/L	0.2035	likely_benign	0.2235	benign	0.288	Stabilizing	0.919	D	0.491	neutral	None	None	None	None	N
R/M	0.2623	likely_benign	0.2961	benign	0.032	Stabilizing	0.999	D	0.527	neutral	None	None	None	None	N
R/N	0.4137	ambiguous	0.471	ambiguous	0.21	Stabilizing	0.919	D	0.45	neutral	None	None	None	None	N
R/P	0.4079	ambiguous	0.4868	ambiguous	0.191	Stabilizing	0.988	D	0.539	neutral	None	None	None	None	N
R/Q	0.1031	likely_benign	0.11	benign	0.061	Stabilizing	0.919	D	0.477	neutral	None	None	None	None	N
R/S	0.345	ambiguous	0.3838	ambiguous	-0.123	Destabilizing	0.896	D	0.496	neutral	N	0.436084784	None	None	N
R/T	0.205	likely_benign	0.2264	benign	0.022	Stabilizing	0.896	D	0.499	neutral	N	0.453769254	None	None	N
R/V	0.2891	likely_benign	0.3068	benign	0.191	Stabilizing	0.988	D	0.521	neutral	None	None	None	None	N
R/W	0.2163	likely_benign	0.2581	benign	-0.479	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
R/Y	0.3656	ambiguous	0.4317	ambiguous	-0.071	Destabilizing	0.996	D	0.551	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.