TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9308	28147;28148;28149	chr2:178711314;178711313;178711312	chr2:179576041;179576040;179576039
N2AB	8991	27196;27197;27198	chr2:178711314;178711313;178711312	chr2:179576041;179576040;179576039
N2A	8064	24415;24416;24417	chr2:178711314;178711313;178711312	chr2:179576041;179576040;179576039
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-79
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7965
• 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
R/K	None	None	0.002	N	0.143	0.102	0.201204373187	gnomAD-4.0.0	6.85874E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01313E-07	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	0.355	ambiguous	0.3398	benign	0.146	Stabilizing	0.329	N	0.338	neutral	None	None	None	None	I
R/C	0.3022	likely_benign	0.2782	benign	-0.035	Destabilizing	0.995	D	0.355	neutral	None	None	None	None	I
R/D	0.6391	likely_pathogenic	0.6085	pathogenic	-0.127	Destabilizing	0.704	D	0.459	neutral	None	None	None	None	I
R/E	0.351	ambiguous	0.3073	benign	-0.053	Destabilizing	0.329	N	0.363	neutral	None	None	None	None	I
R/F	0.5691	likely_pathogenic	0.5383	ambiguous	-0.024	Destabilizing	0.981	D	0.391	neutral	None	None	None	None	I
R/G	0.2201	likely_benign	0.2161	benign	-0.057	Destabilizing	0.425	N	0.391	neutral	N	0.484517922	None	None	I
R/H	0.1164	likely_benign	0.1135	benign	-0.634	Destabilizing	0.981	D	0.431	neutral	None	None	None	None	I
R/I	0.3036	likely_benign	0.2697	benign	0.649	Stabilizing	0.863	D	0.409	neutral	N	0.484771412	None	None	I
R/K	0.0933	likely_benign	0.0944	benign	0.039	Stabilizing	0.002	N	0.143	neutral	N	0.419885967	None	None	I
R/L	0.2532	likely_benign	0.2384	benign	0.649	Stabilizing	0.495	N	0.407	neutral	None	None	None	None	I
R/M	0.2765	likely_benign	0.2523	benign	0.093	Stabilizing	0.981	D	0.408	neutral	None	None	None	None	I
R/N	0.5066	ambiguous	0.4847	ambiguous	0.2	Stabilizing	0.704	D	0.369	neutral	None	None	None	None	I
R/P	0.6211	likely_pathogenic	0.6696	pathogenic	0.502	Stabilizing	0.828	D	0.439	neutral	None	None	None	None	I
R/Q	0.1144	likely_benign	0.1068	benign	0.161	Stabilizing	0.704	D	0.428	neutral	None	None	None	None	I
R/S	0.4176	ambiguous	0.396	ambiguous	-0.041	Destabilizing	0.065	N	0.172	neutral	N	0.453481253	None	None	I
R/T	0.2228	likely_benign	0.2054	benign	0.167	Stabilizing	0.01	N	0.145	neutral	N	0.467623986	None	None	I
R/V	0.3895	ambiguous	0.3565	ambiguous	0.502	Stabilizing	0.704	D	0.467	neutral	None	None	None	None	I
R/W	0.1797	likely_benign	0.1685	benign	-0.127	Destabilizing	0.995	D	0.36	neutral	None	None	None	None	I
R/Y	0.4341	ambiguous	0.4102	ambiguous	0.285	Stabilizing	0.981	D	0.411	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.