TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25337	76234;76235;76236	chr2:178570123;178570122;178570121	chr2:179434850;179434849;179434848
N2AB	23696	71311;71312;71313	chr2:178570123;178570122;178570121	chr2:179434850;179434849;179434848
N2A	22769	68530;68531;68532	chr2:178570123;178570122;178570121	chr2:179434850;179434849;179434848
N2B	16272	49039;49040;49041	chr2:178570123;178570122;178570121	chr2:179434850;179434849;179434848
Novex-1	16397	49414;49415;49416	chr2:178570123;178570122;178570121	chr2:179434850;179434849;179434848
Novex-2	16464	49615;49616;49617	chr2:178570123;178570122;178570121	chr2:179434850;179434849;179434848
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-72
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4651
• 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
L/I	rs764447275	-0.438	0.801	N	0.286	0.142	0.402899589544	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.57E-05	0
L/I	rs764447275	-0.438	0.801	N	0.286	0.142	0.402899589544	gnomAD-4.0.0	6.36734E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.14373E-05	0	0
L/P	None	None	0.966	N	0.387	0.415	0.783275769904	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
L/A	0.1002	likely_benign	0.125	benign	-0.873	Destabilizing	0.525	D	0.305	neutral	None	None	None	None	I
L/C	0.3469	ambiguous	0.4008	ambiguous	-0.669	Destabilizing	0.998	D	0.351	neutral	None	None	None	None	I
L/D	0.474	ambiguous	0.4787	ambiguous	-0.339	Destabilizing	0.842	D	0.36	neutral	None	None	None	None	I
L/E	0.2357	likely_benign	0.254	benign	-0.419	Destabilizing	0.728	D	0.319	neutral	None	None	None	None	I
L/F	0.1165	likely_benign	0.1365	benign	-0.754	Destabilizing	0.966	D	0.387	neutral	N	0.494703733	None	None	I
L/G	0.2897	likely_benign	0.3367	benign	-1.071	Destabilizing	0.842	D	0.369	neutral	None	None	None	None	I
L/H	0.1347	likely_benign	0.154	benign	-0.245	Destabilizing	0.028	N	0.325	neutral	N	0.474219621	None	None	I
L/I	0.0672	likely_benign	0.0768	benign	-0.46	Destabilizing	0.801	D	0.286	neutral	N	0.43157468	None	None	I
L/K	0.1793	likely_benign	0.1907	benign	-0.52	Destabilizing	0.728	D	0.297	neutral	None	None	None	None	I
L/M	0.0821	likely_benign	0.0994	benign	-0.428	Destabilizing	0.991	D	0.4	neutral	None	None	None	None	I
L/N	0.1841	likely_benign	0.2013	benign	-0.29	Destabilizing	0.842	D	0.361	neutral	None	None	None	None	I
L/P	0.5882	likely_pathogenic	0.5917	pathogenic	-0.564	Destabilizing	0.966	D	0.387	neutral	N	0.506313528	None	None	I
L/Q	0.0987	likely_benign	0.1107	benign	-0.533	Destabilizing	0.172	N	0.266	neutral	None	None	None	None	I
L/R	0.1453	likely_benign	0.1492	benign	0.107	Stabilizing	0.801	D	0.329	neutral	N	0.515267925	None	None	I
L/S	0.1046	likely_benign	0.1247	benign	-0.79	Destabilizing	0.728	D	0.299	neutral	None	None	None	None	I
L/T	0.0705	likely_benign	0.0872	benign	-0.76	Destabilizing	0.029	N	0.159	neutral	None	None	None	None	I
L/V	0.0735	likely_benign	0.084	benign	-0.564	Destabilizing	0.454	N	0.305	neutral	N	0.487907966	None	None	I
L/W	0.2523	likely_benign	0.2604	benign	-0.745	Destabilizing	0.998	D	0.39	neutral	None	None	None	None	I
L/Y	0.2866	likely_benign	0.3185	benign	-0.518	Destabilizing	0.949	D	0.371	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.