TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17033	51322;51323;51324	chr2:178611032;178611031;178611030	chr2:179475759;179475758;179475757
N2AB	15392	46399;46400;46401	chr2:178611032;178611031;178611030	chr2:179475759;179475758;179475757
N2A	14465	43618;43619;43620	chr2:178611032;178611031;178611030	chr2:179475759;179475758;179475757
N2B	7968	24127;24128;24129	chr2:178611032;178611031;178611030	chr2:179475759;179475758;179475757
Novex-1	8093	24502;24503;24504	chr2:178611032;178611031;178611030	chr2:179475759;179475758;179475757
Novex-2	8160	24703;24704;24705	chr2:178611032;178611031;178611030	chr2:179475759;179475758;179475757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-111
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.6652
• 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/V	None	None	0.174	N	0.454	0.057	0.243972157842	gnomAD-4.0.0	1.59379E-06	None	None	None	None	I	None	0	0	None	0	2.77917E-05	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
L/A	0.2364	likely_benign	0.2237	benign	-0.467	Destabilizing	0.004	N	0.403	neutral	None	None	None	None	I
L/C	0.5323	ambiguous	0.4557	ambiguous	-0.759	Destabilizing	0.973	D	0.586	neutral	None	None	None	None	I
L/D	0.7229	likely_pathogenic	0.6899	pathogenic	-0.266	Destabilizing	0.704	D	0.614	neutral	None	None	None	None	I
L/E	0.4426	ambiguous	0.4223	ambiguous	-0.365	Destabilizing	0.826	D	0.605	neutral	None	None	None	None	I
L/F	0.1804	likely_benign	0.1797	benign	-0.623	Destabilizing	0.782	D	0.446	neutral	N	0.511387921	None	None	I
L/G	0.5663	likely_pathogenic	0.51	ambiguous	-0.574	Destabilizing	0.404	N	0.582	neutral	None	None	None	None	I
L/H	0.2769	likely_benign	0.2351	benign	0.083	Stabilizing	0.965	D	0.647	neutral	N	0.517194395	None	None	I
L/I	0.1098	likely_benign	0.111	benign	-0.308	Destabilizing	0.007	N	0.288	neutral	N	0.506839445	None	None	I
L/K	0.3919	ambiguous	0.3549	ambiguous	-0.342	Destabilizing	0.826	D	0.562	neutral	None	None	None	None	I
L/M	0.1285	likely_benign	0.13	benign	-0.533	Destabilizing	0.826	D	0.465	neutral	None	None	None	None	I
L/N	0.3701	ambiguous	0.3706	ambiguous	-0.194	Destabilizing	0.018	N	0.495	neutral	None	None	None	None	I
L/P	0.7786	likely_pathogenic	0.6958	pathogenic	-0.332	Destabilizing	0.879	D	0.639	neutral	D	0.689580296	None	None	I
L/Q	0.2046	likely_benign	0.176	benign	-0.395	Destabilizing	0.906	D	0.625	neutral	None	None	None	None	I
L/R	0.3046	likely_benign	0.2427	benign	0.162	Stabilizing	0.782	D	0.625	neutral	D	0.626594814	None	None	I
L/S	0.3082	likely_benign	0.2832	benign	-0.58	Destabilizing	0.404	N	0.585	neutral	None	None	None	None	I
L/T	0.2481	likely_benign	0.2388	benign	-0.576	Destabilizing	0.575	D	0.517	neutral	None	None	None	None	I
L/V	0.1242	likely_benign	0.121	benign	-0.332	Destabilizing	0.174	N	0.454	neutral	N	0.503908881	None	None	I
L/W	0.3344	likely_benign	0.2451	benign	-0.641	Destabilizing	0.991	D	0.682	prob.neutral	None	None	None	None	I
L/Y	0.3723	ambiguous	0.3489	ambiguous	-0.399	Destabilizing	0.967	D	0.54	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.