TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5162	15709;15710;15711	chr2:178734340;178734339;178734338	chr2:179599067;179599066;179599065
N2AB	4845	14758;14759;14760	chr2:178734340;178734339;178734338	chr2:179599067;179599066;179599065
N2A	3918	11977;11978;11979	chr2:178734340;178734339;178734338	chr2:179599067;179599066;179599065
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-34
• Domain position: 88
• Structural Position: 177
• Q(SASA): 0.2205
• 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
H/Q	None	None	None	N	0.251	0.076	0.0986583533028	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
H/R	rs761387658	-0.793	0.025	N	0.475	0.157	0.170165803431	gnomAD-2.1.1	4.17E-06	None	None	None	None	N	None	0	3.02E-05	None	0	0	None	0	None	0	0	0
H/R	rs761387658	-0.793	0.025	N	0.475	0.157	0.170165803431	gnomAD-4.0.0	3.27872E-06	None	None	None	None	N	None	0	2.37327E-05	None	0	0	None	0	0	2.94897E-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
H/A	0.2546	likely_benign	0.3557	ambiguous	-1.839	Destabilizing	None	N	0.237	neutral	None	None	None	None	N
H/C	0.1136	likely_benign	0.1459	benign	-1.017	Destabilizing	0.781	D	0.516	neutral	None	None	None	None	N
H/D	0.5168	ambiguous	0.6696	pathogenic	-1.759	Destabilizing	0.049	N	0.47	neutral	N	0.45920018	None	None	N
H/E	0.4608	ambiguous	0.5863	pathogenic	-1.546	Destabilizing	0.033	N	0.383	neutral	None	None	None	None	N
H/F	0.1385	likely_benign	0.2251	benign	0.071	Stabilizing	None	N	0.223	neutral	None	None	None	None	N
H/G	0.3977	ambiguous	0.5049	ambiguous	-2.285	Highly Destabilizing	0.015	N	0.383	neutral	None	None	None	None	N
H/I	0.1685	likely_benign	0.2103	benign	-0.511	Destabilizing	0.033	N	0.495	neutral	None	None	None	None	N
H/K	0.4771	ambiguous	0.5452	ambiguous	-0.973	Destabilizing	0.033	N	0.425	neutral	None	None	None	None	N
H/L	0.0872	likely_benign	0.0927	benign	-0.511	Destabilizing	0.011	N	0.418	neutral	N	0.455437902	None	None	N
H/M	0.3375	likely_benign	0.4062	ambiguous	-0.746	Destabilizing	0.54	D	0.501	neutral	None	None	None	None	N
H/N	0.1447	likely_benign	0.1941	benign	-1.848	Destabilizing	0.049	N	0.478	neutral	N	0.45920018	None	None	N
H/P	0.2808	likely_benign	0.3713	ambiguous	-0.945	Destabilizing	0.202	N	0.476	neutral	N	0.459594217	None	None	N
H/Q	0.2146	likely_benign	0.3	benign	-1.476	Destabilizing	None	N	0.251	neutral	N	0.458103889	None	None	N
H/R	0.2071	likely_benign	0.2559	benign	-1.137	Destabilizing	0.025	N	0.475	neutral	N	0.458777434	None	None	N
H/S	0.2423	likely_benign	0.3379	benign	-2.015	Highly Destabilizing	0.015	N	0.375	neutral	None	None	None	None	N
H/T	0.2513	likely_benign	0.3713	ambiguous	-1.665	Destabilizing	0.064	N	0.41	neutral	None	None	None	None	N
H/V	0.1368	likely_benign	0.1597	benign	-0.945	Destabilizing	0.064	N	0.419	neutral	None	None	None	None	N
H/W	0.3374	likely_benign	0.4393	ambiguous	0.798	Stabilizing	0.54	D	0.479	neutral	None	None	None	None	N
H/Y	0.0537	likely_benign	0.0826	benign	0.539	Stabilizing	None	N	0.15	neutral	N	0.414605133	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.