TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6237	18934;18935;18936	chr2:178729447;178729446;178729445	chr2:179594174;179594173;179594172
N2AB	5920	17983;17984;17985	chr2:178729447;178729446;178729445	chr2:179594174;179594173;179594172
N2A	4993	15202;15203;15204	chr2:178729447;178729446;178729445	chr2:179594174;179594173;179594172
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-46
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.6661
• 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	None	None	0.005	N	0.301	0.201	0.480574121323	gnomAD-4.0.0	1.59166E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	0	0	0	0
R/W	rs750368911	-0.279	0.828	N	0.277	0.409	0.450733807028	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
R/W	rs750368911	-0.279	0.828	N	0.277	0.409	0.450733807028	gnomAD-4.0.0	6.36663E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.1437E-05	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	0.3092	likely_benign	0.3369	benign	0.086	Stabilizing	0.003	N	0.249	neutral	None	None	None	None	N
R/C	0.3156	likely_benign	0.3425	ambiguous	-0.011	Destabilizing	0.628	D	0.279	neutral	None	None	None	None	N
R/D	0.5467	ambiguous	0.5873	pathogenic	-0.154	Destabilizing	0.031	N	0.288	neutral	None	None	None	None	N
R/E	0.2682	likely_benign	0.2708	benign	-0.095	Destabilizing	0.007	N	0.213	neutral	None	None	None	None	N
R/F	0.5541	ambiguous	0.5875	pathogenic	-0.122	Destabilizing	0.628	D	0.358	neutral	None	None	None	None	N
R/G	0.2128	likely_benign	0.2127	benign	-0.105	Destabilizing	0.005	N	0.301	neutral	N	0.487479183	None	None	N
R/H	0.126	likely_benign	0.1385	benign	-0.64	Destabilizing	0.356	N	0.223	neutral	None	None	None	None	N
R/I	0.2343	likely_benign	0.2606	benign	0.553	Stabilizing	0.136	N	0.435	neutral	None	None	None	None	N
R/K	0.0594	likely_benign	0.0596	benign	0.007	Stabilizing	None	N	0.2	neutral	N	0.389525775	None	None	N
R/L	0.2392	likely_benign	0.2543	benign	0.553	Stabilizing	0.031	N	0.28	neutral	None	None	None	None	N
R/M	0.213	likely_benign	0.2228	benign	0.114	Stabilizing	0.56	D	0.281	neutral	N	0.483516158	None	None	N
R/N	0.3977	ambiguous	0.4572	ambiguous	0.238	Stabilizing	0.031	N	0.221	neutral	None	None	None	None	N
R/P	0.8616	likely_pathogenic	0.8678	pathogenic	0.418	Stabilizing	0.136	N	0.365	neutral	None	None	None	None	N
R/Q	0.0975	likely_benign	0.1018	benign	0.151	Stabilizing	0.016	N	0.303	neutral	None	None	None	None	N
R/S	0.3526	ambiguous	0.3912	ambiguous	-0.034	Destabilizing	None	N	0.164	neutral	N	0.473507021	None	None	N
R/T	0.1654	likely_benign	0.1938	benign	0.152	Stabilizing	0.012	N	0.303	neutral	N	0.473317807	None	None	N
R/V	0.2769	likely_benign	0.3085	benign	0.418	Stabilizing	0.031	N	0.318	neutral	None	None	None	None	N
R/W	0.2347	likely_benign	0.2275	benign	-0.213	Destabilizing	0.828	D	0.277	neutral	N	0.493974897	None	None	N
R/Y	0.43	ambiguous	0.4609	ambiguous	0.195	Stabilizing	0.356	N	0.373	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.