TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8440	25543;25544;25545	chr2:178717556;178717555;178717554	chr2:179582283;179582282;179582281
N2AB	8123	24592;24593;24594	chr2:178717556;178717555;178717554	chr2:179582283;179582282;179582281
N2A	7196	21811;21812;21813	chr2:178717556;178717555;178717554	chr2:179582283;179582282;179582281
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-69
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6432
• 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
T/S	rs778495825	0.069	0.001	N	0.107	0.12	0.110078149338	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
T/S	rs778495825	0.069	0.001	N	0.107	0.12	0.110078149338	gnomAD-4.0.0	1.59543E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43728E-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	0.089	likely_benign	0.0866	benign	-0.439	Destabilizing	0.024	N	0.307	neutral	D	0.523783913	None	None	I
T/C	0.5285	ambiguous	0.5178	ambiguous	-0.206	Destabilizing	0.993	D	0.488	neutral	None	None	None	None	I
T/D	0.3755	ambiguous	0.3599	ambiguous	0.043	Stabilizing	0.193	N	0.395	neutral	None	None	None	None	I
T/E	0.2608	likely_benign	0.2534	benign	-0.053	Destabilizing	0.021	N	0.238	neutral	None	None	None	None	I
T/F	0.1816	likely_benign	0.1803	benign	-1.056	Destabilizing	0.977	D	0.547	neutral	None	None	None	None	I
T/G	0.2981	likely_benign	0.2818	benign	-0.523	Destabilizing	0.667	D	0.501	neutral	None	None	None	None	I
T/H	0.2293	likely_benign	0.2147	benign	-0.899	Destabilizing	0.941	D	0.54	neutral	None	None	None	None	I
T/I	0.1597	likely_benign	0.1599	benign	-0.339	Destabilizing	0.923	D	0.457	neutral	D	0.532443469	None	None	I
T/K	0.1808	likely_benign	0.1617	benign	-0.282	Destabilizing	0.527	D	0.395	neutral	None	None	None	None	I
T/L	0.1121	likely_benign	0.1094	benign	-0.339	Destabilizing	0.69	D	0.422	neutral	None	None	None	None	I
T/M	0.086	likely_benign	0.0877	benign	0.007	Stabilizing	0.98	D	0.475	neutral	None	None	None	None	I
T/N	0.117	likely_benign	0.1112	benign	-0.027	Destabilizing	0.153	N	0.33	neutral	D	0.522687835	None	None	I
T/P	0.2919	likely_benign	0.2985	benign	-0.347	Destabilizing	0.72	D	0.445	neutral	N	0.484744958	None	None	I
T/Q	0.2044	likely_benign	0.1909	benign	-0.334	Destabilizing	0.039	N	0.247	neutral	None	None	None	None	I
T/R	0.156	likely_benign	0.1417	benign	-0.006	Destabilizing	0.856	D	0.439	neutral	None	None	None	None	I
T/S	0.1008	likely_benign	0.0978	benign	-0.223	Destabilizing	0.001	N	0.107	neutral	N	0.41796317	None	None	I
T/V	0.1354	likely_benign	0.1339	benign	-0.347	Destabilizing	0.614	D	0.339	neutral	None	None	None	None	I
T/W	0.5611	ambiguous	0.5414	ambiguous	-1.039	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	I
T/Y	0.2519	likely_benign	0.2428	benign	-0.755	Destabilizing	0.992	D	0.546	neutral	None	None	None	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.