TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14755	44488;44489;44490	chr2:178630259;178630258;178630257	chr2:179494986;179494985;179494984
N2AB	13114	39565;39566;39567	chr2:178630259;178630258;178630257	chr2:179494986;179494985;179494984
N2A	12187	36784;36785;36786	chr2:178630259;178630258;178630257	chr2:179494986;179494985;179494984
N2B	5690	17293;17294;17295	chr2:178630259;178630258;178630257	chr2:179494986;179494985;179494984
Novex-1	5815	17668;17669;17670	chr2:178630259;178630258;178630257	chr2:179494986;179494985;179494984
Novex-2	5882	17869;17870;17871	chr2:178630259;178630258;178630257	chr2:179494986;179494985;179494984
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-98
• Domain position: 81
• Structural Position: 166
• Q(SASA): 0.1375
• 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
A/V	None	None	0.999	D	0.617	0.427	0.344017737713	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-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
A/C	0.8225	likely_pathogenic	0.8597	pathogenic	-1.154	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
A/D	0.967	likely_pathogenic	0.9862	pathogenic	-0.999	Destabilizing	1.0	D	0.913	deleterious	D	0.621614355	None	None	N
A/E	0.9783	likely_pathogenic	0.9883	pathogenic	-1.027	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/F	0.969	likely_pathogenic	0.9754	pathogenic	-1.139	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
A/G	0.2392	likely_benign	0.3563	ambiguous	-1.171	Destabilizing	0.999	D	0.618	neutral	N	0.509424579	None	None	N
A/H	0.9858	likely_pathogenic	0.9905	pathogenic	-1.323	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
A/I	0.9596	likely_pathogenic	0.975	pathogenic	-0.37	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
A/K	0.9917	likely_pathogenic	0.9952	pathogenic	-1.045	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
A/L	0.9094	likely_pathogenic	0.9338	pathogenic	-0.37	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/M	0.943	likely_pathogenic	0.9616	pathogenic	-0.384	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/N	0.9613	likely_pathogenic	0.9786	pathogenic	-0.83	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
A/P	0.9914	likely_pathogenic	0.9954	pathogenic	-0.511	Destabilizing	1.0	D	0.876	deleterious	D	0.621762804	None	None	N
A/Q	0.9674	likely_pathogenic	0.9764	pathogenic	-0.981	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/R	0.9682	likely_pathogenic	0.9764	pathogenic	-0.761	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/S	0.2163	likely_benign	0.2923	benign	-1.252	Destabilizing	0.999	D	0.64	neutral	D	0.539611957	None	None	N
A/T	0.557	ambiguous	0.6811	pathogenic	-1.171	Destabilizing	1.0	D	0.671	prob.neutral	N	0.514461059	None	None	N
A/V	0.8002	likely_pathogenic	0.864	pathogenic	-0.511	Destabilizing	0.999	D	0.617	neutral	D	0.550931604	None	None	N
A/W	0.9968	likely_pathogenic	0.9977	pathogenic	-1.437	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/Y	0.9876	likely_pathogenic	0.99	pathogenic	-1.018	Destabilizing	1.0	D	0.914	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.