TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18574	55945;55946;55947	chr2:178601277;178601276;178601275	chr2:179466004;179466003;179466002
N2AB	16933	51022;51023;51024	chr2:178601277;178601276;178601275	chr2:179466004;179466003;179466002
N2A	16006	48241;48242;48243	chr2:178601277;178601276;178601275	chr2:179466004;179466003;179466002
N2B	9509	28750;28751;28752	chr2:178601277;178601276;178601275	chr2:179466004;179466003;179466002
Novex-1	9634	29125;29126;29127	chr2:178601277;178601276;178601275	chr2:179466004;179466003;179466002
Novex-2	9701	29326;29327;29328	chr2:178601277;178601276;178601275	chr2:179466004;179466003;179466002
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-22
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.4574
• 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
R/G	rs2053379995	None	0.999	N	0.656	0.266	0.383590876969	gnomAD-4.0.0	1.23239E-05	None	None	None	None	N	None	0	0	None	0	1.98323E-04	None	0	0	0	0	0
R/S	None	None	0.999	N	0.721	0.223	0.248417906384	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
R/A	0.6399	likely_pathogenic	0.5973	pathogenic	-0.527	Destabilizing	0.998	D	0.55	neutral	None	None	None	None	N
R/C	0.3426	ambiguous	0.2758	benign	-0.394	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
R/D	0.9267	likely_pathogenic	0.9163	pathogenic	-0.047	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
R/E	0.6097	likely_pathogenic	0.56	ambiguous	0.048	Stabilizing	0.998	D	0.654	prob.neutral	None	None	None	None	N
R/F	0.8207	likely_pathogenic	0.8017	pathogenic	-0.548	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
R/G	0.6047	likely_pathogenic	0.5764	pathogenic	-0.804	Destabilizing	0.999	D	0.656	prob.neutral	N	0.484016725	None	None	N
R/H	0.2036	likely_benign	0.1942	benign	-1.233	Destabilizing	0.999	D	0.737	deleterious	None	None	None	None	N
R/I	0.4885	ambiguous	0.4341	ambiguous	0.199	Stabilizing	0.999	D	0.82	deleterious	N	0.510144533	None	None	N
R/K	0.1155	likely_benign	0.1187	benign	-0.557	Destabilizing	0.994	D	0.567	neutral	N	0.448538714	None	None	N
R/L	0.5006	ambiguous	0.4705	ambiguous	0.199	Stabilizing	0.999	D	0.656	prob.neutral	None	None	None	None	N
R/M	0.497	ambiguous	0.481	ambiguous	-0.042	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	N
R/N	0.8418	likely_pathogenic	0.825	pathogenic	0.013	Stabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
R/P	0.9743	likely_pathogenic	0.9748	pathogenic	-0.021	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
R/Q	0.159	likely_benign	0.1413	benign	-0.199	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
R/S	0.7367	likely_pathogenic	0.7034	pathogenic	-0.643	Destabilizing	0.999	D	0.721	deleterious	N	0.458350276	None	None	N
R/T	0.4244	ambiguous	0.3891	ambiguous	-0.384	Destabilizing	0.999	D	0.717	prob.delet.	N	0.493348284	None	None	N
R/V	0.5149	ambiguous	0.4581	ambiguous	-0.021	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
R/W	0.451	ambiguous	0.4112	ambiguous	-0.313	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
R/Y	0.7335	likely_pathogenic	0.6996	pathogenic	0.026	Stabilizing	0.999	D	0.831	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.