TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14949	45070;45071;45072	chr2:178622738;178622737;178622736	chr2:179487465;179487464;179487463
N2AB	13308	40147;40148;40149	chr2:178622738;178622737;178622736	chr2:179487465;179487464;179487463
N2A	12381	37366;37367;37368	chr2:178622738;178622737;178622736	chr2:179487465;179487464;179487463
N2B	5884	17875;17876;17877	chr2:178622738;178622737;178622736	chr2:179487465;179487464;179487463
Novex-1	6009	18250;18251;18252	chr2:178622738;178622737;178622736	chr2:179487465;179487464;179487463
Novex-2	6076	18451;18452;18453	chr2:178622738;178622737;178622736	chr2:179487465;179487464;179487463
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-101
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7191
• 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/A	rs878912840	None	0.454	N	0.297	0.089	0.225215365344	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs878912840	None	0.454	N	0.297	0.089	0.225215365344	gnomAD-4.0.0	6.58666E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47314E-05	0	0
T/S	rs878912840	0.003	0.136	N	0.109	0.063	0.20549828249	gnomAD-2.1.1	4.21E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.28E-06	0
T/S	rs878912840	0.003	0.136	N	0.109	0.063	0.20549828249	gnomAD-4.0.0	6.88067E-07	None	None	None	None	I	None	0	2.27645E-05	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	0.0879	likely_benign	0.0961	benign	-0.52	Destabilizing	0.454	N	0.297	neutral	N	0.47933944	None	None	I
T/C	0.4972	ambiguous	0.5048	ambiguous	-0.385	Destabilizing	0.998	D	0.42	neutral	None	None	None	None	I
T/D	0.3247	likely_benign	0.3723	ambiguous	0.484	Stabilizing	0.525	D	0.36	neutral	None	None	None	None	I
T/E	0.2158	likely_benign	0.2333	benign	0.44	Stabilizing	0.007	N	0.125	neutral	None	None	None	None	I
T/F	0.3182	likely_benign	0.3526	ambiguous	-0.919	Destabilizing	0.974	D	0.444	neutral	None	None	None	None	I
T/G	0.2341	likely_benign	0.2569	benign	-0.683	Destabilizing	0.842	D	0.401	neutral	None	None	None	None	I
T/H	0.2171	likely_benign	0.2332	benign	-0.869	Destabilizing	0.016	N	0.202	neutral	None	None	None	None	I
T/I	0.2132	likely_benign	0.2357	benign	-0.202	Destabilizing	0.966	D	0.427	neutral	D	0.539643304	None	None	I
T/K	0.1436	likely_benign	0.149	benign	-0.308	Destabilizing	0.728	D	0.367	neutral	None	None	None	None	I
T/L	0.1207	likely_benign	0.1336	benign	-0.202	Destabilizing	0.842	D	0.366	neutral	None	None	None	None	I
T/M	0.1129	likely_benign	0.1211	benign	-0.154	Destabilizing	0.991	D	0.407	neutral	None	None	None	None	I
T/N	0.1223	likely_benign	0.1405	benign	-0.18	Destabilizing	0.801	D	0.287	neutral	N	0.50967633	None	None	I
T/P	0.1512	likely_benign	0.1788	benign	-0.278	Destabilizing	0.966	D	0.433	neutral	N	0.511011273	None	None	I
T/Q	0.1687	likely_benign	0.1774	benign	-0.327	Destabilizing	0.728	D	0.401	neutral	None	None	None	None	I
T/R	0.1214	likely_benign	0.122	benign	-0.082	Destabilizing	0.842	D	0.407	neutral	None	None	None	None	I
T/S	0.1125	likely_benign	0.1248	benign	-0.471	Destabilizing	0.136	N	0.109	neutral	N	0.480837424	None	None	I
T/V	0.1686	likely_benign	0.1871	benign	-0.278	Destabilizing	0.915	D	0.281	neutral	None	None	None	None	I
T/W	0.5983	likely_pathogenic	0.6372	pathogenic	-0.901	Destabilizing	0.998	D	0.439	neutral	None	None	None	None	I
T/Y	0.3108	likely_benign	0.3626	ambiguous	-0.618	Destabilizing	0.949	D	0.421	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.