TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9439	28540;28541;28542	chr2:178710782;178710781;178710780	chr2:179575509;179575508;179575507
N2AB	9122	27589;27590;27591	chr2:178710782;178710781;178710780	chr2:179575509;179575508;179575507
N2A	8195	24808;24809;24810	chr2:178710782;178710781;178710780	chr2:179575509;179575508;179575507
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-80
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.9068
• Site annotation: Phosphoserine
• 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
S/N	None	None	0.642	None	0.215	0.265	0.32471235697	gnomAD-4.0.0	4.77295E-06	None	None	Phosphoserine	None	I	None	0	0	None	0	0	None	0	0	8.57324E-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	0.0764	likely_benign	0.0805	benign	-0.175	Destabilizing	0.176	N	0.18	neutral	None	None	Phosphoserine	None	I
S/C	0.1934	likely_benign	0.2507	benign	-0.386	Destabilizing	0.993	D	0.318	neutral	None	None	Phosphoserine	None	I
S/D	0.4031	ambiguous	0.5274	ambiguous	0.289	Stabilizing	0.704	D	0.2	neutral	None	None	Phosphoserine	None	I
S/E	0.4753	ambiguous	0.6269	pathogenic	0.196	Stabilizing	0.704	D	0.187	neutral	None	None	Phosphoserine	None	I
S/F	0.2321	likely_benign	0.2719	benign	-0.866	Destabilizing	0.893	D	0.387	neutral	None	None	Phosphoserine	None	I
S/G	0.0902	likely_benign	0.1099	benign	-0.252	Destabilizing	0.425	N	0.186	neutral	None	None	Phosphoserine	None	I
S/H	0.3241	likely_benign	0.4689	ambiguous	-0.642	Destabilizing	0.981	D	0.321	neutral	None	None	Phosphoserine	None	I
S/I	0.191	likely_benign	0.2467	benign	-0.108	Destabilizing	0.473	N	0.425	neutral	None	None	Phosphoserine	None	I
S/K	0.5255	ambiguous	0.7422	pathogenic	-0.338	Destabilizing	0.031	N	0.165	neutral	None	None	Phosphoserine	None	I
S/L	0.1092	likely_benign	0.1189	benign	-0.108	Destabilizing	0.007	N	0.208	neutral	None	None	Phosphoserine	None	I
S/M	0.2039	likely_benign	0.2712	benign	-0.143	Destabilizing	0.893	D	0.313	neutral	None	None	Phosphoserine	None	I
S/N	0.1316	likely_benign	0.179	benign	-0.166	Destabilizing	0.642	D	0.215	neutral	None	None	Phosphoserine	None	I
S/P	0.0817	likely_benign	0.1131	benign	-0.103	Destabilizing	0.007	N	0.172	neutral	None	None	Phosphoserine	None	I
S/Q	0.4115	ambiguous	0.5896	pathogenic	-0.342	Destabilizing	0.893	D	0.263	neutral	None	None	Phosphoserine	None	I
S/R	0.4605	ambiguous	0.6655	pathogenic	-0.159	Destabilizing	0.473	N	0.359	neutral	None	None	Phosphoserine	None	I
S/T	0.0804	likely_benign	0.0887	benign	-0.249	Destabilizing	0.01	N	0.115	neutral	None	None	Phosphoserine	None	I
S/V	0.1987	likely_benign	0.2462	benign	-0.103	Destabilizing	0.543	D	0.321	neutral	None	None	Phosphoserine	None	I
S/W	0.3186	likely_benign	0.386	ambiguous	-0.947	Destabilizing	0.995	D	0.39	neutral	None	None	Phosphoserine	None	I
S/Y	0.188	likely_benign	0.2373	benign	-0.619	Destabilizing	0.981	D	0.375	neutral	None	None	Phosphoserine	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.