TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5721	17386;17387;17388	chr2:178731714;178731713;178731712	chr2:179596441;179596440;179596439
N2AB	5404	16435;16436;16437	chr2:178731714;178731713;178731712	chr2:179596441;179596440;179596439
N2A	4477	13654;13655;13656	chr2:178731714;178731713;178731712	chr2:179596441;179596440;179596439
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-40
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.2674
• 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/G	None	None	0.081	D	0.441	0.153	0.19670166235	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
S/A	0.075	likely_benign	0.0756	benign	-0.685	Destabilizing	0.055	N	0.367	neutral	None	None	None	None	N
S/C	0.1225	likely_benign	0.1151	benign	-0.457	Destabilizing	0.002	N	0.341	neutral	N	0.51567723	None	None	N
S/D	0.3139	likely_benign	0.2966	benign	-0.375	Destabilizing	None	N	0.203	neutral	None	None	None	None	N
S/E	0.4014	ambiguous	0.3638	ambiguous	-0.376	Destabilizing	0.055	N	0.439	neutral	None	None	None	None	N
S/F	0.1662	likely_benign	0.1629	benign	-0.802	Destabilizing	0.667	D	0.625	neutral	None	None	None	None	N
S/G	0.0842	likely_benign	0.0811	benign	-0.947	Destabilizing	0.081	N	0.441	neutral	D	0.524421418	None	None	N
S/H	0.2459	likely_benign	0.2162	benign	-1.413	Destabilizing	0.001	N	0.286	neutral	None	None	None	None	N
S/I	0.142	likely_benign	0.1417	benign	-0.095	Destabilizing	0.272	N	0.642	neutral	D	0.534465053	None	None	N
S/K	0.4174	ambiguous	0.3672	ambiguous	-0.786	Destabilizing	0.22	N	0.494	neutral	None	None	None	None	N
S/L	0.0968	likely_benign	0.0971	benign	-0.095	Destabilizing	0.124	N	0.569	neutral	None	None	None	None	N
S/M	0.1978	likely_benign	0.1845	benign	0.152	Stabilizing	0.667	D	0.571	neutral	None	None	None	None	N
S/N	0.1078	likely_benign	0.1037	benign	-0.709	Destabilizing	0.175	N	0.485	neutral	N	0.501717917	None	None	N
S/P	0.3488	ambiguous	0.3223	benign	-0.257	Destabilizing	0.364	N	0.589	neutral	None	None	None	None	N
S/Q	0.3769	ambiguous	0.3303	benign	-0.845	Destabilizing	0.497	N	0.558	neutral	None	None	None	None	N
S/R	0.3244	likely_benign	0.284	benign	-0.664	Destabilizing	0.175	N	0.589	neutral	N	0.521303755	None	None	N
S/T	0.0705	likely_benign	0.0688	benign	-0.697	Destabilizing	0.001	N	0.209	neutral	N	0.489017978	None	None	N
S/V	0.1477	likely_benign	0.1467	benign	-0.257	Destabilizing	0.124	N	0.589	neutral	None	None	None	None	N
S/W	0.3399	likely_benign	0.3108	benign	-0.798	Destabilizing	0.958	D	0.676	prob.neutral	None	None	None	None	N
S/Y	0.1655	likely_benign	0.1568	benign	-0.541	Destabilizing	0.497	N	0.639	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.