TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30022	90289;90290;90291	chr2:178552836;178552835;178552834	chr2:179417563;179417562;179417561
N2AB	28381	85366;85367;85368	chr2:178552836;178552835;178552834	chr2:179417563;179417562;179417561
N2A	27454	82585;82586;82587	chr2:178552836;178552835;178552834	chr2:179417563;179417562;179417561
N2B	20957	63094;63095;63096	chr2:178552836;178552835;178552834	chr2:179417563;179417562;179417561
Novex-1	21082	63469;63470;63471	chr2:178552836;178552835;178552834	chr2:179417563;179417562;179417561
Novex-2	21149	63670;63671;63672	chr2:178552836;178552835;178552834	chr2:179417563;179417562;179417561
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-106
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.739
• 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
T/I	rs771515515	0.112	0.257	N	0.565	0.149	0.340273420219	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs771515515	0.112	0.257	N	0.565	0.149	0.340273420219	gnomAD-4.0.0	2.02984E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40984E-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
T/A	0.0569	likely_benign	0.0547	benign	-0.157	Destabilizing	None	N	0.068	neutral	N	0.447077276	None	None	N
T/C	0.3023	likely_benign	0.298	benign	-0.468	Destabilizing	0.914	D	0.44	neutral	None	None	None	None	N
T/D	0.2391	likely_benign	0.2315	benign	-0.009	Destabilizing	0.061	N	0.479	neutral	None	None	None	None	N
T/E	0.1784	likely_benign	0.1716	benign	-0.095	Destabilizing	0.002	N	0.176	neutral	None	None	None	None	N
T/F	0.1762	likely_benign	0.1709	benign	-0.84	Destabilizing	0.739	D	0.619	neutral	None	None	None	None	N
T/G	0.1351	likely_benign	0.1308	benign	-0.209	Destabilizing	0.026	N	0.399	neutral	None	None	None	None	N
T/H	0.1966	likely_benign	0.194	benign	-0.312	Destabilizing	0.482	N	0.502	neutral	None	None	None	None	N
T/I	0.091	likely_benign	0.0904	benign	-0.143	Destabilizing	0.257	N	0.565	neutral	N	0.494425719	None	None	N
T/K	0.1232	likely_benign	0.1203	benign	-0.306	Destabilizing	None	N	0.175	neutral	N	0.420392107	None	None	N
T/L	0.0634	likely_benign	0.0627	benign	-0.143	Destabilizing	0.116	N	0.465	neutral	None	None	None	None	N
T/M	0.0708	likely_benign	0.0722	benign	-0.273	Destabilizing	0.739	D	0.461	neutral	None	None	None	None	N
T/N	0.0912	likely_benign	0.093	benign	-0.175	Destabilizing	0.116	N	0.291	neutral	None	None	None	None	N
T/P	0.0695	likely_benign	0.0653	benign	-0.124	Destabilizing	0.167	N	0.55	neutral	N	0.459065139	None	None	N
T/Q	0.1496	likely_benign	0.1463	benign	-0.348	Destabilizing	0.061	N	0.55	neutral	None	None	None	None	N
T/R	0.1173	likely_benign	0.1127	benign	-0.012	Destabilizing	0.047	N	0.535	neutral	N	0.518708088	None	None	N
T/S	0.0797	likely_benign	0.0805	benign	-0.322	Destabilizing	0.001	N	0.069	neutral	N	0.384335307	None	None	N
T/V	0.0768	likely_benign	0.0757	benign	-0.124	Destabilizing	0.061	N	0.349	neutral	None	None	None	None	N
T/W	0.4713	ambiguous	0.4512	ambiguous	-0.951	Destabilizing	0.914	D	0.521	neutral	None	None	None	None	N
T/Y	0.2242	likely_benign	0.2201	benign	-0.619	Destabilizing	0.739	D	0.602	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.