TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18259	55000;55001;55002	chr2:178603912;178603911;178603910	chr2:179468639;179468638;179468637
N2AB	16618	50077;50078;50079	chr2:178603912;178603911;178603910	chr2:179468639;179468638;179468637
N2A	15691	47296;47297;47298	chr2:178603912;178603911;178603910	chr2:179468639;179468638;179468637
N2B	9194	27805;27806;27807	chr2:178603912;178603911;178603910	chr2:179468639;179468638;179468637
Novex-1	9319	28180;28181;28182	chr2:178603912;178603911;178603910	chr2:179468639;179468638;179468637
Novex-2	9386	28381;28382;28383	chr2:178603912;178603911;178603910	chr2:179468639;179468638;179468637
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-20
• Domain position: 94
• Structural Position: 122
• Q(SASA): 0.7031
• 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
E/K	None	None	0.919	N	0.561	0.198	0.278143212241	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
E/A	0.1359	likely_benign	0.1231	benign	-0.359	Destabilizing	0.132	N	0.403	neutral	N	0.494583222	None	None	N
E/C	0.7759	likely_pathogenic	0.7924	pathogenic	-0.223	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
E/D	0.0978	likely_benign	0.0937	benign	-0.4	Destabilizing	0.919	D	0.565	neutral	N	0.485558307	None	None	N
E/F	0.6947	likely_pathogenic	0.6448	pathogenic	-0.134	Destabilizing	0.997	D	0.822	deleterious	None	None	None	None	N
E/G	0.1721	likely_benign	0.1556	benign	-0.562	Destabilizing	0.851	D	0.543	neutral	N	0.478077054	None	None	N
E/H	0.4721	ambiguous	0.4365	ambiguous	0.226	Stabilizing	0.999	D	0.593	neutral	None	None	None	None	N
E/I	0.265	likely_benign	0.2412	benign	0.143	Stabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
E/K	0.1617	likely_benign	0.1426	benign	0.234	Stabilizing	0.919	D	0.561	neutral	N	0.500143757	None	None	N
E/L	0.264	likely_benign	0.2234	benign	0.143	Stabilizing	0.981	D	0.571	neutral	None	None	None	None	N
E/M	0.3703	ambiguous	0.3344	benign	0.115	Stabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
E/N	0.2553	likely_benign	0.2275	benign	-0.169	Destabilizing	0.981	D	0.562	neutral	None	None	None	None	N
E/P	0.2567	likely_benign	0.2477	benign	-0.004	Destabilizing	0.991	D	0.641	neutral	None	None	None	None	N
E/Q	0.1393	likely_benign	0.1293	benign	-0.118	Destabilizing	0.988	D	0.622	neutral	N	0.521519107	None	None	N
E/R	0.2899	likely_benign	0.2577	benign	0.538	Stabilizing	0.991	D	0.58	neutral	None	None	None	None	N
E/S	0.1841	likely_benign	0.168	benign	-0.322	Destabilizing	0.37	N	0.288	neutral	None	None	None	None	N
E/T	0.2178	likely_benign	0.1953	benign	-0.152	Destabilizing	0.883	D	0.619	neutral	None	None	None	None	N
E/V	0.1669	likely_benign	0.1553	benign	-0.004	Destabilizing	0.976	D	0.543	neutral	N	0.472191705	None	None	N
E/W	0.8858	likely_pathogenic	0.8655	pathogenic	0.039	Stabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
E/Y	0.5367	ambiguous	0.5026	ambiguous	0.112	Stabilizing	0.997	D	0.814	deleterious	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.