TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32791	98596;98597;98598	chr2:178539694;178539693;178539692	chr2:179404421;179404420;179404419
N2AB	31150	93673;93674;93675	chr2:178539694;178539693;178539692	chr2:179404421;179404420;179404419
N2A	30223	90892;90893;90894	chr2:178539694;178539693;178539692	chr2:179404421;179404420;179404419
N2B	23726	71401;71402;71403	chr2:178539694;178539693;178539692	chr2:179404421;179404420;179404419
Novex-1	23851	71776;71777;71778	chr2:178539694;178539693;178539692	chr2:179404421;179404420;179404419
Novex-2	23918	71977;71978;71979	chr2:178539694;178539693;178539692	chr2:179404421;179404420;179404419
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-155
• Domain position: 84
• Structural Position: 175
• Q(SASA): 0.6698
• 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/S	None	None	0.062	N	0.431	0.093	0.250579442822	gnomAD-4.0.0	6.84227E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65645E-05
R/T	None	None	0.117	N	0.444	0.08	0.254761474806	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	0.3559	ambiguous	0.4003	ambiguous	-0.488	Destabilizing	0.035	N	0.435	neutral	None	None	None	None	N
R/C	0.2373	likely_benign	0.2357	benign	-0.654	Destabilizing	0.001	N	0.393	neutral	None	None	None	None	N
R/D	0.5769	likely_pathogenic	0.6226	pathogenic	0.078	Stabilizing	0.149	N	0.433	neutral	None	None	None	None	N
R/E	0.3057	likely_benign	0.3334	benign	0.199	Stabilizing	0.081	N	0.381	neutral	None	None	None	None	N
R/F	0.6266	likely_pathogenic	0.647	pathogenic	-0.483	Destabilizing	0.791	D	0.423	neutral	None	None	None	None	N
R/G	0.3426	ambiguous	0.3649	ambiguous	-0.752	Destabilizing	0.117	N	0.467	neutral	N	0.489491445	None	None	N
R/H	0.1135	likely_benign	0.1106	benign	-1.121	Destabilizing	0.555	D	0.445	neutral	None	None	None	None	N
R/I	0.282	likely_benign	0.3102	benign	0.202	Stabilizing	0.555	D	0.429	neutral	None	None	None	None	N
R/K	0.069	likely_benign	0.0733	benign	-0.372	Destabilizing	None	N	0.167	neutral	N	0.418000455	None	None	N
R/L	0.2734	likely_benign	0.3021	benign	0.202	Stabilizing	0.149	N	0.453	neutral	None	None	None	None	N
R/M	0.232	likely_benign	0.2623	benign	-0.313	Destabilizing	0.741	D	0.433	neutral	N	0.489998424	None	None	N
R/N	0.4018	ambiguous	0.4387	ambiguous	-0.191	Destabilizing	0.149	N	0.423	neutral	None	None	None	None	N
R/P	0.9237	likely_pathogenic	0.9359	pathogenic	-0.008	Destabilizing	0.555	D	0.41	neutral	None	None	None	None	N
R/Q	0.1005	likely_benign	0.1028	benign	-0.252	Destabilizing	0.081	N	0.434	neutral	None	None	None	None	N
R/S	0.3824	ambiguous	0.4213	ambiguous	-0.813	Destabilizing	0.062	N	0.431	neutral	N	0.479993063	None	None	N
R/T	0.1612	likely_benign	0.1941	benign	-0.513	Destabilizing	0.117	N	0.444	neutral	N	0.4497848	None	None	N
R/V	0.3288	likely_benign	0.3694	ambiguous	-0.008	Destabilizing	0.149	N	0.467	neutral	None	None	None	None	N
R/W	0.2585	likely_benign	0.2662	benign	-0.334	Destabilizing	0.915	D	0.469	neutral	N	0.490251913	None	None	N
R/Y	0.4811	ambiguous	0.4936	ambiguous	0.013	Stabilizing	0.791	D	0.425	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.