TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29492	88699;88700;88701	chr2:178554985;178554984;178554983	chr2:179419712;179419711;179419710
N2AB	27851	83776;83777;83778	chr2:178554985;178554984;178554983	chr2:179419712;179419711;179419710
N2A	26924	80995;80996;80997	chr2:178554985;178554984;178554983	chr2:179419712;179419711;179419710
N2B	20427	61504;61505;61506	chr2:178554985;178554984;178554983	chr2:179419712;179419711;179419710
Novex-1	20552	61879;61880;61881	chr2:178554985;178554984;178554983	chr2:179419712;179419711;179419710
Novex-2	20619	62080;62081;62082	chr2:178554985;178554984;178554983	chr2:179419712;179419711;179419710
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-146
• Domain position: 49
• Structural Position: 130
• Q(SASA): 0.4343
• 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	0.055	N	0.351	0.108	0.318828661733	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	0
T/S	rs1700819240	None	0.001	N	0.168	0.106	0.264547087235	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/S	rs1700819240	None	0.001	N	0.168	0.106	0.264547087235	gnomAD-4.0.0	6.57341E-06	None	None	None	None	N	None	2.41313E-05	0	None	0	0	None	0	0	0	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	0.1054	likely_benign	0.0982	benign	-0.392	Destabilizing	0.055	N	0.351	neutral	N	0.497792177	None	None	N
T/C	0.456	ambiguous	0.426	ambiguous	-0.192	Destabilizing	0.909	D	0.48	neutral	None	None	None	None	N
T/D	0.3094	likely_benign	0.277	benign	0.28	Stabilizing	0.157	N	0.349	neutral	None	None	None	None	N
T/E	0.3452	ambiguous	0.3183	benign	0.215	Stabilizing	0.157	N	0.365	neutral	None	None	None	None	N
T/F	0.438	ambiguous	0.3925	ambiguous	-0.85	Destabilizing	0.726	D	0.563	neutral	None	None	None	None	N
T/G	0.1789	likely_benign	0.178	benign	-0.541	Destabilizing	0.157	N	0.413	neutral	None	None	None	None	N
T/H	0.2952	likely_benign	0.2864	benign	-0.833	Destabilizing	0.909	D	0.577	neutral	None	None	None	None	N
T/I	0.3817	ambiguous	0.3332	benign	-0.116	Destabilizing	0.497	N	0.418	neutral	D	0.530173955	None	None	N
T/K	0.224	likely_benign	0.2059	benign	-0.307	Destabilizing	0.005	N	0.243	neutral	None	None	None	None	N
T/L	0.2026	likely_benign	0.1879	benign	-0.116	Destabilizing	0.272	N	0.369	neutral	None	None	None	None	N
T/M	0.1434	likely_benign	0.1378	benign	0.074	Stabilizing	0.968	D	0.453	neutral	None	None	None	None	N
T/N	0.1154	likely_benign	0.1083	benign	-0.111	Destabilizing	0.124	N	0.316	neutral	N	0.510027969	None	None	N
T/P	0.424	ambiguous	0.4106	ambiguous	-0.179	Destabilizing	0.497	N	0.414	neutral	D	0.536099849	None	None	N
T/Q	0.2531	likely_benign	0.2463	benign	-0.314	Destabilizing	0.567	D	0.415	neutral	None	None	None	None	N
T/R	0.2042	likely_benign	0.1896	benign	-0.061	Destabilizing	0.396	N	0.363	neutral	None	None	None	None	N
T/S	0.0876	likely_benign	0.0842	benign	-0.346	Destabilizing	0.001	N	0.168	neutral	N	0.468373347	None	None	N
T/V	0.2716	likely_benign	0.2406	benign	-0.179	Destabilizing	0.272	N	0.332	neutral	None	None	None	None	N
T/W	0.7268	likely_pathogenic	0.7109	pathogenic	-0.854	Destabilizing	0.968	D	0.619	neutral	None	None	None	None	N
T/Y	0.3937	ambiguous	0.3621	ambiguous	-0.566	Destabilizing	0.726	D	0.555	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.