TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15350	46273;46274;46275	chr2:178620473;178620472;178620471	chr2:179485200;179485199;179485198
N2AB	13709	41350;41351;41352	chr2:178620473;178620472;178620471	chr2:179485200;179485199;179485198
N2A	12782	38569;38570;38571	chr2:178620473;178620472;178620471	chr2:179485200;179485199;179485198
N2B	6285	19078;19079;19080	chr2:178620473;178620472;178620471	chr2:179485200;179485199;179485198
Novex-1	6410	19453;19454;19455	chr2:178620473;178620472;178620471	chr2:179485200;179485199;179485198
Novex-2	6477	19654;19655;19656	chr2:178620473;178620472;178620471	chr2:179485200;179485199;179485198
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: Ig-105
• Domain position: 49
• Structural Position: 125
• Q(SASA): 0.5226
• 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	0.896	D	0.56	0.34	0.38342384377	gnomAD-4.0.0	3.42373E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50014E-06	0	0
R/K	None	None	0.011	N	0.165	0.203	0.284150004643	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	0.4011	ambiguous	0.3586	ambiguous	-0.063	Destabilizing	0.919	D	0.567	neutral	None	None	None	None	N
R/C	0.2617	likely_benign	0.2309	benign	-0.168	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
R/D	0.6904	likely_pathogenic	0.6606	pathogenic	0.039	Stabilizing	0.976	D	0.591	neutral	None	None	None	None	N
R/E	0.3965	ambiguous	0.361	ambiguous	0.114	Stabilizing	0.851	D	0.516	neutral	None	None	None	None	N
R/F	0.5759	likely_pathogenic	0.548	ambiguous	-0.244	Destabilizing	0.996	D	0.672	neutral	None	None	None	None	N
R/G	0.3306	likely_benign	0.2989	benign	-0.276	Destabilizing	0.896	D	0.56	neutral	D	0.530081428	None	None	N
R/H	0.1215	likely_benign	0.0979	benign	-0.777	Destabilizing	0.996	D	0.55	neutral	None	None	None	None	N
R/I	0.2616	likely_benign	0.2199	benign	0.468	Stabilizing	0.984	D	0.685	prob.neutral	N	0.490398531	None	None	N
R/K	0.0989	likely_benign	0.0917	benign	-0.054	Destabilizing	0.011	N	0.165	neutral	N	0.481147208	None	None	N
R/L	0.3001	likely_benign	0.2596	benign	0.468	Stabilizing	0.919	D	0.56	neutral	None	None	None	None	N
R/M	0.2767	likely_benign	0.249	benign	0.036	Stabilizing	0.999	D	0.619	neutral	None	None	None	None	N
R/N	0.5568	ambiguous	0.5463	ambiguous	0.212	Stabilizing	0.976	D	0.545	neutral	None	None	None	None	N
R/P	0.9437	likely_pathogenic	0.934	pathogenic	0.312	Stabilizing	0.988	D	0.672	neutral	None	None	None	None	N
R/Q	0.1276	likely_benign	0.1054	benign	0.101	Stabilizing	0.976	D	0.579	neutral	None	None	None	None	N
R/S	0.4323	ambiguous	0.3946	ambiguous	-0.216	Destabilizing	0.896	D	0.587	neutral	N	0.502936284	None	None	N
R/T	0.2012	likely_benign	0.18	benign	0.005	Stabilizing	0.896	D	0.586	neutral	N	0.491827498	None	None	N
R/V	0.351	ambiguous	0.2907	benign	0.312	Stabilizing	0.988	D	0.661	neutral	None	None	None	None	N
R/W	0.2418	likely_benign	0.2351	benign	-0.251	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
R/Y	0.4905	ambiguous	0.4718	ambiguous	0.156	Stabilizing	0.996	D	0.671	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.