TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23537	70834;70835;70836	chr2:178575523;178575522;178575521	chr2:179440250;179440249;179440248
N2AB	21896	65911;65912;65913	chr2:178575523;178575522;178575521	chr2:179440250;179440249;179440248
N2A	20969	63130;63131;63132	chr2:178575523;178575522;178575521	chr2:179440250;179440249;179440248
N2B	14472	43639;43640;43641	chr2:178575523;178575522;178575521	chr2:179440250;179440249;179440248
Novex-1	14597	44014;44015;44016	chr2:178575523;178575522;178575521	chr2:179440250;179440249;179440248
Novex-2	14664	44215;44216;44217	chr2:178575523;178575522;178575521	chr2:179440250;179440249;179440248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-59
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.3548
• 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
D/V	rs1193472633	0.213	0.638	N	0.759	0.288	0.504968073517	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-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
D/A	0.1371	likely_benign	0.136	benign	-0.478	Destabilizing	0.201	N	0.719	prob.delet.	N	0.446733347	None	None	N
D/C	0.5872	likely_pathogenic	0.6086	pathogenic	-0.244	Destabilizing	0.982	D	0.772	deleterious	None	None	None	None	N
D/E	0.087	likely_benign	0.0864	benign	-0.662	Destabilizing	0.001	N	0.229	neutral	N	0.417794519	None	None	N
D/F	0.5496	ambiguous	0.5448	ambiguous	-0.215	Destabilizing	0.935	D	0.781	deleterious	None	None	None	None	N
D/G	0.1684	likely_benign	0.1663	benign	-0.777	Destabilizing	0.334	N	0.693	prob.neutral	N	0.350244163	None	None	N
D/H	0.3033	likely_benign	0.3028	benign	-0.49	Destabilizing	0.931	D	0.745	deleterious	N	0.485945096	None	None	N
D/I	0.2698	likely_benign	0.2548	benign	0.294	Stabilizing	0.826	D	0.783	deleterious	None	None	None	None	N
D/K	0.3272	likely_benign	0.3366	benign	-0.404	Destabilizing	0.25	N	0.661	neutral	None	None	None	None	N
D/L	0.2802	likely_benign	0.2789	benign	0.294	Stabilizing	0.7	D	0.761	deleterious	None	None	None	None	N
D/M	0.5011	ambiguous	0.4819	ambiguous	0.59	Stabilizing	0.982	D	0.771	deleterious	None	None	None	None	N
D/N	0.1232	likely_benign	0.1136	benign	-0.7	Destabilizing	0.334	N	0.658	neutral	N	0.463414953	None	None	N
D/P	0.486	ambiguous	0.5417	ambiguous	0.061	Stabilizing	0.826	D	0.754	deleterious	None	None	None	None	N
D/Q	0.258	likely_benign	0.2569	benign	-0.604	Destabilizing	0.539	D	0.676	prob.neutral	None	None	None	None	N
D/R	0.3951	ambiguous	0.3941	ambiguous	-0.221	Destabilizing	0.539	D	0.767	deleterious	None	None	None	None	N
D/S	0.121	likely_benign	0.1148	benign	-0.89	Destabilizing	0.25	N	0.609	neutral	None	None	None	None	N
D/T	0.2022	likely_benign	0.201	benign	-0.66	Destabilizing	0.7	D	0.723	prob.delet.	None	None	None	None	N
D/V	0.1657	likely_benign	0.1548	benign	0.061	Stabilizing	0.638	D	0.759	deleterious	N	0.453891392	None	None	N
D/W	0.8702	likely_pathogenic	0.8818	pathogenic	-0.074	Destabilizing	0.982	D	0.739	prob.delet.	None	None	None	None	N
D/Y	0.2646	likely_benign	0.2538	benign	-0.006	Destabilizing	0.916	D	0.781	deleterious	N	0.446157344	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.