TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23514	70765;70766;70767	chr2:178575592;178575591;178575590	chr2:179440319;179440318;179440317
N2AB	21873	65842;65843;65844	chr2:178575592;178575591;178575590	chr2:179440319;179440318;179440317
N2A	20946	63061;63062;63063	chr2:178575592;178575591;178575590	chr2:179440319;179440318;179440317
N2B	14449	43570;43571;43572	chr2:178575592;178575591;178575590	chr2:179440319;179440318;179440317
Novex-1	14574	43945;43946;43947	chr2:178575592;178575591;178575590	chr2:179440319;179440318;179440317
Novex-2	14641	44146;44147;44148	chr2:178575592;178575591;178575590	chr2:179440319;179440318;179440317
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-58
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.4825
• Predicted PPI site: I

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
E/K	None	None	0.538	N	0.431	0.235	0.218845423259	gnomAD-4.0.0	6.84261E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99549E-07	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
E/A	0.3835	ambiguous	0.4315	ambiguous	-0.503	Destabilizing	0.557	D	0.501	neutral	N	0.503472064	None	None	I
E/C	0.9643	likely_pathogenic	0.9693	pathogenic	-0.138	Destabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	I
E/D	0.3106	likely_benign	0.3305	benign	-0.346	Destabilizing	None	N	0.212	neutral	N	0.514401134	None	None	I
E/F	0.9674	likely_pathogenic	0.9755	pathogenic	-0.291	Destabilizing	0.996	D	0.616	neutral	None	None	None	None	I
E/G	0.6497	likely_pathogenic	0.7082	pathogenic	-0.698	Destabilizing	0.807	D	0.511	neutral	N	0.469373186	None	None	I
E/H	0.8704	likely_pathogenic	0.8958	pathogenic	0.027	Stabilizing	0.983	D	0.342	neutral	None	None	None	None	I
E/I	0.5698	likely_pathogenic	0.6261	pathogenic	-0.018	Destabilizing	0.911	D	0.625	neutral	None	None	None	None	I
E/K	0.4494	ambiguous	0.5208	ambiguous	0.302	Stabilizing	0.538	D	0.431	neutral	N	0.459009211	None	None	I
E/L	0.7854	likely_pathogenic	0.8202	pathogenic	-0.018	Destabilizing	0.835	D	0.593	neutral	None	None	None	None	I
E/M	0.7562	likely_pathogenic	0.8081	pathogenic	0.081	Stabilizing	0.874	D	0.597	neutral	None	None	None	None	I
E/N	0.6593	likely_pathogenic	0.6978	pathogenic	-0.114	Destabilizing	0.702	D	0.381	neutral	None	None	None	None	I
E/P	0.8673	likely_pathogenic	0.8905	pathogenic	-0.16	Destabilizing	0.604	D	0.473	neutral	None	None	None	None	I
E/Q	0.3417	ambiguous	0.3891	ambiguous	-0.06	Destabilizing	0.049	N	0.309	neutral	N	0.468722212	None	None	I
E/R	0.652	likely_pathogenic	0.6991	pathogenic	0.547	Stabilizing	0.844	D	0.366	neutral	None	None	None	None	I
E/S	0.558	ambiguous	0.6086	pathogenic	-0.258	Destabilizing	0.625	D	0.411	neutral	None	None	None	None	I
E/T	0.5221	ambiguous	0.576	pathogenic	-0.087	Destabilizing	0.89	D	0.442	neutral	None	None	None	None	I
E/V	0.4664	ambiguous	0.5194	ambiguous	-0.16	Destabilizing	0.731	D	0.549	neutral	N	0.466595845	None	None	I
E/W	0.9938	likely_pathogenic	0.9954	pathogenic	-0.089	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
E/Y	0.9394	likely_pathogenic	0.952	pathogenic	-0.035	Destabilizing	0.994	D	0.589	neutral	None	None	None	None	I

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.