TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25276	76051;76052;76053	chr2:178570306;178570305;178570304	chr2:179435033;179435032;179435031
N2AB	23635	71128;71129;71130	chr2:178570306;178570305;178570304	chr2:179435033;179435032;179435031
N2A	22708	68347;68348;68349	chr2:178570306;178570305;178570304	chr2:179435033;179435032;179435031
N2B	16211	48856;48857;48858	chr2:178570306;178570305;178570304	chr2:179435033;179435032;179435031
Novex-1	16336	49231;49232;49233	chr2:178570306;178570305;178570304	chr2:179435033;179435032;179435031
Novex-2	16403	49432;49433;49434	chr2:178570306;178570305;178570304	chr2:179435033;179435032;179435031
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: Fn3-71
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.0973
• 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	rs748746031	-0.729	None	N	0.319	0.127	0.16115917748	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
T/I	rs748746031	-0.729	None	N	0.319	0.127	0.16115917748	gnomAD-4.0.0	1.59235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02682E-05

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	0.0847	likely_benign	0.0815	benign	-2.062	Highly Destabilizing	None	N	0.23	neutral	N	0.480117989	None	None	N
T/C	0.1859	likely_benign	0.1949	benign	-1.299	Destabilizing	0.018	N	0.668	neutral	None	None	None	None	N
T/D	0.5288	ambiguous	0.5037	ambiguous	-2.237	Highly Destabilizing	0.003	N	0.617	neutral	None	None	None	None	N
T/E	0.3205	likely_benign	0.3094	benign	-1.97	Destabilizing	0.003	N	0.543	neutral	None	None	None	None	N
T/F	0.1381	likely_benign	0.1459	benign	-1.377	Destabilizing	0.001	N	0.585	neutral	None	None	None	None	N
T/G	0.2495	likely_benign	0.2605	benign	-2.444	Highly Destabilizing	0.003	N	0.58	neutral	None	None	None	None	N
T/H	0.2108	likely_benign	0.1969	benign	-2.081	Highly Destabilizing	0.116	N	0.685	prob.neutral	None	None	None	None	N
T/I	0.0412	likely_benign	0.0434	benign	-1.003	Destabilizing	None	N	0.319	neutral	N	0.378551059	None	None	N
T/K	0.1976	likely_benign	0.1849	benign	-0.859	Destabilizing	0.003	N	0.545	neutral	None	None	None	None	N
T/L	0.0421	likely_benign	0.0427	benign	-1.003	Destabilizing	None	N	0.34	neutral	None	None	None	None	N
T/M	0.0569	likely_benign	0.0582	benign	-1.296	Destabilizing	0.002	N	0.632	neutral	None	None	None	None	N
T/N	0.1369	likely_benign	0.1333	benign	-1.558	Destabilizing	0.018	N	0.564	neutral	N	0.482848863	None	None	N
T/P	0.6972	likely_pathogenic	0.6804	pathogenic	-1.337	Destabilizing	0.008	N	0.631	neutral	N	0.485704512	None	None	N
T/Q	0.1958	likely_benign	0.1881	benign	-1.19	Destabilizing	0.023	N	0.635	neutral	None	None	None	None	N
T/R	0.1554	likely_benign	0.1498	benign	-1.119	Destabilizing	0.008	N	0.629	neutral	None	None	None	None	N
T/S	0.1058	likely_benign	0.1057	benign	-1.825	Destabilizing	0.001	N	0.42	neutral	N	0.458433208	None	None	N
T/V	0.047	likely_benign	0.0512	benign	-1.337	Destabilizing	None	N	0.219	neutral	None	None	None	None	N
T/W	0.5142	ambiguous	0.5067	ambiguous	-1.546	Destabilizing	0.316	N	0.684	prob.neutral	None	None	None	None	N
T/Y	0.197	likely_benign	0.1915	benign	-1.261	Destabilizing	0.003	N	0.667	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.