TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17728	53407;53408;53409	chr2:178607506;178607505;178607504	chr2:179472233;179472232;179472231
N2AB	16087	48484;48485;48486	chr2:178607506;178607505;178607504	chr2:179472233;179472232;179472231
N2A	15160	45703;45704;45705	chr2:178607506;178607505;178607504	chr2:179472233;179472232;179472231
N2B	8663	26212;26213;26214	chr2:178607506;178607505;178607504	chr2:179472233;179472232;179472231
Novex-1	8788	26587;26588;26589	chr2:178607506;178607505;178607504	chr2:179472233;179472232;179472231
Novex-2	8855	26788;26789;26790	chr2:178607506;178607505;178607504	chr2:179472233;179472232;179472231
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: Ig-113
• Domain position: 52
• Structural Position: 137
• Q(SASA): 0.2265
• 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	0.055	N	0.379	0.26	0.236890367714	gnomAD-4.0.0	6.84391E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6575E-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
E/A	0.2956	likely_benign	0.3305	benign	-0.949	Destabilizing	0.012	N	0.463	neutral	N	0.450403662	None	None	N
E/C	0.8479	likely_pathogenic	0.8625	pathogenic	-0.681	Destabilizing	0.864	D	0.583	neutral	None	None	None	None	N
E/D	0.3202	likely_benign	0.3919	ambiguous	-1.618	Destabilizing	None	N	0.177	neutral	N	0.468162704	None	None	N
E/F	0.7946	likely_pathogenic	0.8078	pathogenic	-0.613	Destabilizing	None	N	0.476	neutral	None	None	None	None	N
E/G	0.4676	ambiguous	0.5294	ambiguous	-1.361	Destabilizing	0.055	N	0.491	neutral	N	0.45244389	None	None	N
E/H	0.6442	likely_pathogenic	0.6679	pathogenic	-0.963	Destabilizing	0.356	N	0.544	neutral	None	None	None	None	N
E/I	0.3622	ambiguous	0.3825	ambiguous	0.197	Stabilizing	None	N	0.399	neutral	None	None	None	None	N
E/K	0.3928	ambiguous	0.4198	ambiguous	-1.101	Destabilizing	0.055	N	0.379	neutral	N	0.403919224	None	None	N
E/L	0.5215	ambiguous	0.5443	ambiguous	0.197	Stabilizing	None	N	0.411	neutral	None	None	None	None	N
E/M	0.5039	ambiguous	0.5214	ambiguous	0.759	Stabilizing	0.214	N	0.564	neutral	None	None	None	None	N
E/N	0.4607	ambiguous	0.5265	ambiguous	-1.488	Destabilizing	0.038	N	0.461	neutral	None	None	None	None	N
E/P	0.9909	likely_pathogenic	0.9936	pathogenic	-0.164	Destabilizing	0.356	N	0.589	neutral	None	None	None	None	N
E/Q	0.2449	likely_benign	0.2487	benign	-1.27	Destabilizing	0.055	N	0.477	neutral	N	0.439898667	None	None	N
E/R	0.5682	likely_pathogenic	0.5968	pathogenic	-0.953	Destabilizing	0.214	N	0.503	neutral	None	None	None	None	N
E/S	0.3163	likely_benign	0.3633	ambiguous	-1.962	Destabilizing	0.016	N	0.338	neutral	None	None	None	None	N
E/T	0.2747	likely_benign	0.3096	benign	-1.601	Destabilizing	0.001	N	0.299	neutral	None	None	None	None	N
E/V	0.2164	likely_benign	0.2217	benign	-0.164	Destabilizing	None	N	0.355	neutral	N	0.413482857	None	None	N
E/W	0.9409	likely_pathogenic	0.9444	pathogenic	-0.58	Destabilizing	0.864	D	0.603	neutral	None	None	None	None	N
E/Y	0.732	likely_pathogenic	0.7495	pathogenic	-0.401	Destabilizing	0.12	N	0.599	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.