TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31982	96169;96170;96171	chr2:178544285;178544284;178544283	chr2:179409012;179409011;179409010
N2AB	30341	91246;91247;91248	chr2:178544285;178544284;178544283	chr2:179409012;179409011;179409010
N2A	29414	88465;88466;88467	chr2:178544285;178544284;178544283	chr2:179409012;179409011;179409010
N2B	22917	68974;68975;68976	chr2:178544285;178544284;178544283	chr2:179409012;179409011;179409010
Novex-1	23042	69349;69350;69351	chr2:178544285;178544284;178544283	chr2:179409012;179409011;179409010
Novex-2	23109	69550;69551;69552	chr2:178544285;178544284;178544283	chr2:179409012;179409011;179409010
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-121
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.0953
• 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
S/F	None	None	0.602	N	0.73	0.273	0.514587094315	gnomAD-4.0.0	1.36845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.799E-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
S/A	0.0742	likely_benign	0.0762	benign	-0.865	Destabilizing	0.019	N	0.49	neutral	N	0.469015561	None	None	N
S/C	0.063	likely_benign	0.0644	benign	-0.39	Destabilizing	0.002	N	0.611	neutral	N	0.476789682	None	None	N
S/D	0.3515	ambiguous	0.3632	ambiguous	-1.446	Destabilizing	0.22	N	0.691	prob.neutral	None	None	None	None	N
S/E	0.387	ambiguous	0.3922	ambiguous	-1.207	Destabilizing	0.055	N	0.609	neutral	None	None	None	None	N
S/F	0.1227	likely_benign	0.1247	benign	-0.542	Destabilizing	0.602	D	0.73	prob.delet.	N	0.441156956	None	None	N
S/G	0.0921	likely_benign	0.0947	benign	-1.28	Destabilizing	0.104	N	0.609	neutral	None	None	None	None	N
S/H	0.142	likely_benign	0.1407	benign	-1.46	Destabilizing	0.667	D	0.732	prob.delet.	None	None	None	None	N
S/I	0.0862	likely_benign	0.0876	benign	0.217	Stabilizing	0.497	N	0.754	deleterious	None	None	None	None	N
S/K	0.2708	likely_benign	0.2726	benign	0.019	Stabilizing	0.055	N	0.619	neutral	None	None	None	None	N
S/L	0.0738	likely_benign	0.0753	benign	0.217	Stabilizing	0.055	N	0.712	prob.delet.	None	None	None	None	N
S/M	0.1398	likely_benign	0.1497	benign	-0.039	Destabilizing	0.667	D	0.732	prob.delet.	None	None	None	None	N
S/N	0.0947	likely_benign	0.1004	benign	-0.755	Destabilizing	0.22	N	0.679	prob.neutral	None	None	None	None	N
S/P	0.8997	likely_pathogenic	0.8812	pathogenic	-0.111	Destabilizing	0.602	D	0.777	deleterious	N	0.469700171	None	None	N
S/Q	0.2516	likely_benign	0.2477	benign	-0.403	Destabilizing	0.004	N	0.527	neutral	None	None	None	None	N
S/R	0.1891	likely_benign	0.1814	benign	-0.493	Destabilizing	None	N	0.436	neutral	None	None	None	None	N
S/T	0.0693	likely_benign	0.0727	benign	-0.395	Destabilizing	0.001	N	0.291	neutral	N	0.425645999	None	None	N
S/V	0.1061	likely_benign	0.1088	benign	-0.111	Destabilizing	0.124	N	0.731	prob.delet.	None	None	None	None	N
S/W	0.2524	likely_benign	0.2336	benign	-0.872	Destabilizing	0.958	D	0.767	deleterious	None	None	None	None	N
S/Y	0.1084	likely_benign	0.1042	benign	-0.388	Destabilizing	0.822	D	0.729	prob.delet.	N	0.439906162	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.