TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22118	66577;66578;66579	chr2:178582017;178582016;178582015	chr2:179446744;179446743;179446742
N2AB	20477	61654;61655;61656	chr2:178582017;178582016;178582015	chr2:179446744;179446743;179446742
N2A	19550	58873;58874;58875	chr2:178582017;178582016;178582015	chr2:179446744;179446743;179446742
N2B	13053	39382;39383;39384	chr2:178582017;178582016;178582015	chr2:179446744;179446743;179446742
Novex-1	13178	39757;39758;39759	chr2:178582017;178582016;178582015	chr2:179446744;179446743;179446742
Novex-2	13245	39958;39959;39960	chr2:178582017;178582016;178582015	chr2:179446744;179446743;179446742
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: Fn3-48
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4612
• 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/A	None	None	0.001	N	0.139	0.058	0.117506650769	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86036E-06	0	0
T/I	rs751985481	0.053	0.213	N	0.442	0.142	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	1.78E-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
T/A	0.0743	likely_benign	0.0802	benign	-0.634	Destabilizing	0.001	N	0.139	neutral	N	0.506131154	None	None	N
T/C	0.4177	ambiguous	0.4457	ambiguous	-0.386	Destabilizing	0.951	D	0.497	neutral	None	None	None	None	N
T/D	0.5643	likely_pathogenic	0.6087	pathogenic	-0.15	Destabilizing	0.418	N	0.454	neutral	None	None	None	None	N
T/E	0.4853	ambiguous	0.5193	ambiguous	-0.174	Destabilizing	0.264	N	0.438	neutral	None	None	None	None	N
T/F	0.3267	likely_benign	0.3659	ambiguous	-0.788	Destabilizing	0.836	D	0.495	neutral	None	None	None	None	N
T/G	0.1592	likely_benign	0.1887	benign	-0.861	Destabilizing	0.001	N	0.287	neutral	None	None	None	None	N
T/H	0.3705	ambiguous	0.3823	ambiguous	-1.095	Destabilizing	0.836	D	0.498	neutral	None	None	None	None	N
T/I	0.2071	likely_benign	0.2423	benign	-0.131	Destabilizing	0.213	N	0.442	neutral	N	0.470664904	None	None	N
T/K	0.3615	ambiguous	0.363	ambiguous	-0.739	Destabilizing	0.213	N	0.426	neutral	N	0.491353703	None	None	N
T/L	0.1224	likely_benign	0.1363	benign	-0.131	Destabilizing	0.129	N	0.407	neutral	None	None	None	None	N
T/M	0.1155	likely_benign	0.1203	benign	0.039	Stabilizing	0.836	D	0.515	neutral	None	None	None	None	N
T/N	0.1478	likely_benign	0.169	benign	-0.577	Destabilizing	0.418	N	0.306	neutral	None	None	None	None	N
T/P	0.1282	likely_benign	0.1343	benign	-0.267	Destabilizing	0.523	D	0.541	neutral	N	0.513057126	None	None	N
T/Q	0.2947	likely_benign	0.3101	benign	-0.735	Destabilizing	0.022	N	0.283	neutral	None	None	None	None	N
T/R	0.3659	ambiguous	0.3534	ambiguous	-0.456	Destabilizing	0.213	N	0.533	neutral	N	0.509208745	None	None	N
T/S	0.0984	likely_benign	0.1056	benign	-0.804	Destabilizing	0.003	N	0.144	neutral	N	0.458702566	None	None	N
T/V	0.1345	likely_benign	0.1536	benign	-0.267	Destabilizing	0.01	N	0.183	neutral	None	None	None	None	N
T/W	0.7035	likely_pathogenic	0.7333	pathogenic	-0.769	Destabilizing	0.983	D	0.527	neutral	None	None	None	None	N
T/Y	0.3853	ambiguous	0.417	ambiguous	-0.536	Destabilizing	0.94	D	0.504	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.