TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19536	58831;58832;58833	chr2:178593694;178593693;178593692	chr2:179458421;179458420;179458419
N2AB	17895	53908;53909;53910	chr2:178593694;178593693;178593692	chr2:179458421;179458420;179458419
N2A	16968	51127;51128;51129	chr2:178593694;178593693;178593692	chr2:179458421;179458420;179458419
N2B	10471	31636;31637;31638	chr2:178593694;178593693;178593692	chr2:179458421;179458420;179458419
Novex-1	10596	32011;32012;32013	chr2:178593694;178593693;178593692	chr2:179458421;179458420;179458419
Novex-2	10663	32212;32213;32214	chr2:178593694;178593693;178593692	chr2:179458421;179458420;179458419
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: Fn3-29
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.5413
• 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
K/E	None	None	0.961	N	0.459	0.266	0.33340067248	gnomAD-4.0.0	3.18421E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86607E-05	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	0.3898	ambiguous	0.364	ambiguous	-0.01	Destabilizing	0.97	D	0.498	neutral	None	None	None	None	N
K/C	0.7619	likely_pathogenic	0.7667	pathogenic	-0.349	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/D	0.6212	likely_pathogenic	0.572	pathogenic	0.081	Stabilizing	0.996	D	0.54	neutral	None	None	None	None	N
K/E	0.2531	likely_benign	0.2254	benign	0.097	Stabilizing	0.961	D	0.459	neutral	N	0.482075284	None	None	N
K/F	0.837	likely_pathogenic	0.8186	pathogenic	-0.215	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
K/G	0.5049	ambiguous	0.4603	ambiguous	-0.202	Destabilizing	0.985	D	0.484	neutral	None	None	None	None	N
K/H	0.4245	ambiguous	0.408	ambiguous	-0.387	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
K/I	0.4419	ambiguous	0.4451	ambiguous	0.418	Stabilizing	0.998	D	0.617	neutral	N	0.477649435	None	None	N
K/L	0.4698	ambiguous	0.4564	ambiguous	0.418	Stabilizing	0.97	D	0.484	neutral	None	None	None	None	N
K/M	0.3193	likely_benign	0.3062	benign	0.069	Stabilizing	1.0	D	0.573	neutral	None	None	None	None	N
K/N	0.4947	ambiguous	0.447	ambiguous	0.074	Stabilizing	0.994	D	0.49	neutral	N	0.492988498	None	None	N
K/P	0.8664	likely_pathogenic	0.8549	pathogenic	0.303	Stabilizing	0.999	D	0.577	neutral	None	None	None	None	N
K/Q	0.1793	likely_benign	0.1658	benign	-0.039	Destabilizing	0.989	D	0.509	neutral	N	0.474709382	None	None	N
K/R	0.0872	likely_benign	0.0851	benign	-0.082	Destabilizing	0.031	N	0.159	neutral	N	0.452429955	None	None	N
K/S	0.4821	ambiguous	0.4348	ambiguous	-0.387	Destabilizing	0.985	D	0.457	neutral	None	None	None	None	N
K/T	0.2296	likely_benign	0.2035	benign	-0.221	Destabilizing	0.98	D	0.535	neutral	N	0.464412243	None	None	N
K/V	0.3879	ambiguous	0.3731	ambiguous	0.303	Stabilizing	0.996	D	0.526	neutral	None	None	None	None	N
K/W	0.8552	likely_pathogenic	0.8477	pathogenic	-0.266	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/Y	0.7202	likely_pathogenic	0.7146	pathogenic	0.091	Stabilizing	0.999	D	0.612	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.