TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14729	44410;44411;44412	chr2:178630337;178630336;178630335	chr2:179495064;179495063;179495062
N2AB	13088	39487;39488;39489	chr2:178630337;178630336;178630335	chr2:179495064;179495063;179495062
N2A	12161	36706;36707;36708	chr2:178630337;178630336;178630335	chr2:179495064;179495063;179495062
N2B	5664	17215;17216;17217	chr2:178630337;178630336;178630335	chr2:179495064;179495063;179495062
Novex-1	5789	17590;17591;17592	chr2:178630337;178630336;178630335	chr2:179495064;179495063;179495062
Novex-2	5856	17791;17792;17793	chr2:178630337;178630336;178630335	chr2:179495064;179495063;179495062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-98
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1372
• 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/R	rs774485726	-0.913	0.999	N	0.765	0.458	0.311079019809	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
H/R	rs774485726	-0.913	0.999	N	0.765	0.458	0.311079019809	gnomAD-4.0.0	1.37065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80009E-06	0	0
H/Y	None	None	0.997	N	0.584	0.444	0.299770980665	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
H/A	0.9413	likely_pathogenic	0.9498	pathogenic	-1.943	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
H/C	0.4809	ambiguous	0.5532	ambiguous	-1.276	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
H/D	0.9718	likely_pathogenic	0.9755	pathogenic	-1.864	Destabilizing	0.999	D	0.791	deleterious	D	0.6065461	None	None	N
H/E	0.9769	likely_pathogenic	0.9783	pathogenic	-1.641	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
H/F	0.6509	likely_pathogenic	0.7014	pathogenic	0.026	Stabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
H/G	0.9653	likely_pathogenic	0.9695	pathogenic	-2.38	Highly Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
H/I	0.8694	likely_pathogenic	0.8838	pathogenic	-0.629	Destabilizing	0.999	D	0.907	deleterious	None	None	None	None	N
H/K	0.8791	likely_pathogenic	0.9139	pathogenic	-1.068	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
H/L	0.5333	ambiguous	0.583	pathogenic	-0.629	Destabilizing	0.999	D	0.885	deleterious	D	0.56116367	None	None	N
H/M	0.9373	likely_pathogenic	0.9445	pathogenic	-0.956	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
H/N	0.6808	likely_pathogenic	0.7192	pathogenic	-1.926	Destabilizing	0.997	D	0.547	neutral	D	0.6065461	None	None	N
H/P	0.9463	likely_pathogenic	0.9494	pathogenic	-1.06	Destabilizing	0.999	D	0.889	deleterious	D	0.6065461	None	None	N
H/Q	0.8387	likely_pathogenic	0.8514	pathogenic	-1.493	Destabilizing	0.999	D	0.818	deleterious	D	0.604826485	None	None	N
H/R	0.5138	ambiguous	0.6113	pathogenic	-1.139	Destabilizing	0.999	D	0.765	deleterious	N	0.486588015	None	None	N
H/S	0.894	likely_pathogenic	0.8975	pathogenic	-2.156	Highly Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
H/T	0.9497	likely_pathogenic	0.9546	pathogenic	-1.803	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
H/V	0.8458	likely_pathogenic	0.8763	pathogenic	-1.06	Destabilizing	0.999	D	0.906	deleterious	None	None	None	None	N
H/W	0.7625	likely_pathogenic	0.7967	pathogenic	0.7	Stabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
H/Y	0.2428	likely_benign	0.3196	benign	0.447	Stabilizing	0.997	D	0.584	neutral	N	0.513363785	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.