TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2658	8197;8198;8199	chr2:178771355;178771354;178771353	chr2:179636082;179636081;179636080
N2AB	2658	8197;8198;8199	chr2:178771355;178771354;178771353	chr2:179636082;179636081;179636080
N2A	2658	8197;8198;8199	chr2:178771355;178771354;178771353	chr2:179636082;179636081;179636080
N2B	2612	8059;8060;8061	chr2:178771355;178771354;178771353	chr2:179636082;179636081;179636080
Novex-1	2612	8059;8060;8061	chr2:178771355;178771354;178771353	chr2:179636082;179636081;179636080
Novex-2	2612	8059;8060;8061	chr2:178771355;178771354;178771353	chr2:179636082;179636081;179636080
Novex-3	2658	8197;8198;8199	chr2:178771355;178771354;178771353	chr2:179636082;179636081;179636080

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-16
• Domain position: 38
• Structural Position: 56
• Q(SASA): 0.5173
• 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/L	None	None	0.014	N	0.341	0.234	0.325533332567	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
H/Q	rs1158775069	None	0.001	N	0.131	0.058	0.0986583533028	gnomAD-4.0.0	1.59059E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85659E-06	0	0
H/Y	rs1023349406	None	0.065	N	0.306	0.172	0.284150004643	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.083	likely_benign	0.1067	benign	0.204	Stabilizing	0.002	N	0.263	neutral	None	None	None	None	N
H/C	0.1349	likely_benign	0.1543	benign	0.766	Stabilizing	0.497	N	0.375	neutral	None	None	None	None	N
H/D	0.0967	likely_benign	0.1247	benign	-0.204	Destabilizing	0.003	N	0.277	neutral	N	0.446789174	None	None	N
H/E	0.1164	likely_benign	0.1447	benign	-0.153	Destabilizing	None	N	0.099	neutral	None	None	None	None	N
H/F	0.1948	likely_benign	0.2206	benign	1.135	Stabilizing	0.085	N	0.416	neutral	None	None	None	None	N
H/G	0.1577	likely_benign	0.1914	benign	-0.114	Destabilizing	0.008	N	0.295	neutral	None	None	None	None	N
H/I	0.114	likely_benign	0.1392	benign	1.04	Stabilizing	0.085	N	0.479	neutral	None	None	None	None	N
H/K	0.1047	likely_benign	0.1222	benign	0.146	Stabilizing	0.004	N	0.232	neutral	None	None	None	None	N
H/L	0.0648	likely_benign	0.0744	benign	1.04	Stabilizing	0.014	N	0.341	neutral	N	0.380162884	None	None	N
H/M	0.2087	likely_benign	0.2552	benign	0.746	Stabilizing	0.497	N	0.387	neutral	None	None	None	None	N
H/N	0.0628	likely_benign	0.0757	benign	0.07	Stabilizing	0.014	N	0.201	neutral	N	0.432796477	None	None	N
H/P	0.0453	likely_benign	0.0497	benign	0.786	Stabilizing	None	N	0.139	neutral	N	0.263480797	None	None	N
H/Q	0.0833	likely_benign	0.104	benign	0.239	Stabilizing	0.001	N	0.131	neutral	N	0.414317451	None	None	N
H/R	0.0695	likely_benign	0.0789	benign	-0.578	Destabilizing	None	N	0.132	neutral	N	0.394473007	None	None	N
H/S	0.0868	likely_benign	0.1051	benign	0.246	Stabilizing	0.001	N	0.141	neutral	None	None	None	None	N
H/T	0.0944	likely_benign	0.126	benign	0.399	Stabilizing	0.004	N	0.304	neutral	None	None	None	None	N
H/V	0.0925	likely_benign	0.1128	benign	0.786	Stabilizing	0.018	N	0.397	neutral	None	None	None	None	N
H/W	0.3327	likely_benign	0.3532	ambiguous	1.187	Stabilizing	0.788	D	0.363	neutral	None	None	None	None	N
H/Y	0.0837	likely_benign	0.0896	benign	1.376	Stabilizing	0.065	N	0.306	neutral	N	0.478388083	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.