TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22178	66757;66758;66759	chr2:178581736;178581735;178581734	chr2:179446463;179446462;179446461
N2AB	20537	61834;61835;61836	chr2:178581736;178581735;178581734	chr2:179446463;179446462;179446461
N2A	19610	59053;59054;59055	chr2:178581736;178581735;178581734	chr2:179446463;179446462;179446461
N2B	13113	39562;39563;39564	chr2:178581736;178581735;178581734	chr2:179446463;179446462;179446461
Novex-1	13238	39937;39938;39939	chr2:178581736;178581735;178581734	chr2:179446463;179446462;179446461
Novex-2	13305	40138;40139;40140	chr2:178581736;178581735;178581734	chr2:179446463;179446462;179446461
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-49
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.2422
• 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
G/D	None	None	0.801	N	0.482	0.194	0.230578612272	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0
G/S	None	None	0.022	N	0.153	0.136	0.141422826196	gnomAD-4.0.0	1.60301E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87606E-06	0	0
G/V	None	None	0.801	N	0.557	0.226	0.430239905395	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.1745	likely_benign	0.1623	benign	-0.488	Destabilizing	0.454	N	0.391	neutral	N	0.381817864	None	None	I
G/C	0.2631	likely_benign	0.2628	benign	-0.616	Destabilizing	0.997	D	0.612	neutral	N	0.44238632	None	None	I
G/D	0.6533	likely_pathogenic	0.6716	pathogenic	-1.577	Destabilizing	0.801	D	0.482	neutral	N	0.404211934	None	None	I
G/E	0.5374	ambiguous	0.5674	pathogenic	-1.49	Destabilizing	0.842	D	0.535	neutral	None	None	None	None	I
G/F	0.8206	likely_pathogenic	0.8106	pathogenic	-0.646	Destabilizing	0.991	D	0.639	neutral	None	None	None	None	I
G/H	0.7076	likely_pathogenic	0.7203	pathogenic	-1.647	Destabilizing	0.998	D	0.581	neutral	None	None	None	None	I
G/I	0.4164	ambiguous	0.4217	ambiguous	0.338	Stabilizing	0.949	D	0.609	neutral	None	None	None	None	I
G/K	0.8035	likely_pathogenic	0.8311	pathogenic	-1.134	Destabilizing	0.842	D	0.533	neutral	None	None	None	None	I
G/L	0.5538	ambiguous	0.5585	ambiguous	0.338	Stabilizing	0.842	D	0.54	neutral	None	None	None	None	I
G/M	0.5173	ambiguous	0.5153	ambiguous	0.25	Stabilizing	0.998	D	0.613	neutral	None	None	None	None	I
G/N	0.3977	ambiguous	0.3988	ambiguous	-1.072	Destabilizing	0.842	D	0.467	neutral	None	None	None	None	I
G/P	0.9706	likely_pathogenic	0.9694	pathogenic	0.108	Stabilizing	0.974	D	0.579	neutral	None	None	None	None	I
G/Q	0.5515	ambiguous	0.573	pathogenic	-1.018	Destabilizing	0.974	D	0.596	neutral	None	None	None	None	I
G/R	0.7149	likely_pathogenic	0.7422	pathogenic	-1.134	Destabilizing	0.934	D	0.577	neutral	N	0.41800795	None	None	I
G/S	0.1078	likely_benign	0.102	benign	-1.335	Destabilizing	0.022	N	0.153	neutral	N	0.335042637	None	None	I
G/T	0.1569	likely_benign	0.149	benign	-1.144	Destabilizing	0.029	N	0.299	neutral	None	None	None	None	I
G/V	0.3001	likely_benign	0.2919	benign	0.108	Stabilizing	0.801	D	0.557	neutral	N	0.419778819	None	None	I
G/W	0.7306	likely_pathogenic	0.7519	pathogenic	-1.387	Destabilizing	0.998	D	0.618	neutral	None	None	None	None	I
G/Y	0.7205	likely_pathogenic	0.7209	pathogenic	-0.762	Destabilizing	0.991	D	0.632	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.