TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25464	76615;76616;76617	chr2:178569742;178569741;178569740	chr2:179434469;179434468;179434467
N2AB	23823	71692;71693;71694	chr2:178569742;178569741;178569740	chr2:179434469;179434468;179434467
N2A	22896	68911;68912;68913	chr2:178569742;178569741;178569740	chr2:179434469;179434468;179434467
N2B	16399	49420;49421;49422	chr2:178569742;178569741;178569740	chr2:179434469;179434468;179434467
Novex-1	16524	49795;49796;49797	chr2:178569742;178569741;178569740	chr2:179434469;179434468;179434467
Novex-2	16591	49996;49997;49998	chr2:178569742;178569741;178569740	chr2:179434469;179434468;179434467
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: Fn3-73
• Domain position: 60
• Structural Position: 89
• Q(SASA): 0.3648
• 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/R	None	None	0.997	N	0.663	0.36	0.478755181577	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
T/A	0.0936	likely_benign	0.0973	benign	-0.984	Destabilizing	0.76	D	0.455	neutral	N	0.491957212	None	None	N
T/C	0.3013	likely_benign	0.3188	benign	-0.492	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
T/D	0.4261	ambiguous	0.422	ambiguous	0.054	Stabilizing	0.998	D	0.653	neutral	None	None	None	None	N
T/E	0.3006	likely_benign	0.3111	benign	0.156	Stabilizing	0.993	D	0.618	neutral	None	None	None	None	N
T/F	0.3193	likely_benign	0.3341	benign	-0.98	Destabilizing	0.986	D	0.695	prob.neutral	None	None	None	None	N
T/G	0.2359	likely_benign	0.235	benign	-1.312	Destabilizing	0.993	D	0.625	neutral	None	None	None	None	N
T/H	0.2876	likely_benign	0.2821	benign	-1.336	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
T/I	0.2062	likely_benign	0.2455	benign	-0.166	Destabilizing	0.885	D	0.473	neutral	N	0.503313517	None	None	N
T/K	0.1534	likely_benign	0.1577	benign	-0.223	Destabilizing	0.991	D	0.607	neutral	N	0.465877239	None	None	N
T/L	0.0872	likely_benign	0.0966	benign	-0.166	Destabilizing	0.06	N	0.395	neutral	None	None	None	None	N
T/M	0.0796	likely_benign	0.0811	benign	-0.141	Destabilizing	0.986	D	0.672	neutral	None	None	None	None	N
T/N	0.1025	likely_benign	0.0928	benign	-0.538	Destabilizing	0.998	D	0.557	neutral	None	None	None	None	N
T/P	0.1032	likely_benign	0.1016	benign	-0.407	Destabilizing	0.997	D	0.656	neutral	N	0.460432736	None	None	N
T/Q	0.1821	likely_benign	0.1861	benign	-0.468	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
T/R	0.1396	likely_benign	0.1401	benign	-0.22	Destabilizing	0.997	D	0.663	neutral	N	0.470370237	None	None	N
T/S	0.1271	likely_benign	0.1253	benign	-0.936	Destabilizing	0.969	D	0.422	neutral	N	0.473003583	None	None	N
T/V	0.1507	likely_benign	0.1788	benign	-0.407	Destabilizing	0.06	N	0.405	neutral	None	None	None	None	N
T/W	0.6208	likely_pathogenic	0.6354	pathogenic	-0.958	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
T/Y	0.3019	likely_benign	0.3059	benign	-0.636	Destabilizing	0.998	D	0.7	prob.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.