TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22365	67318;67319;67320	chr2:178580194;178580193;178580192	chr2:179444921;179444920;179444919
N2AB	20724	62395;62396;62397	chr2:178580194;178580193;178580192	chr2:179444921;179444920;179444919
N2A	19797	59614;59615;59616	chr2:178580194;178580193;178580192	chr2:179444921;179444920;179444919
N2B	13300	40123;40124;40125	chr2:178580194;178580193;178580192	chr2:179444921;179444920;179444919
Novex-1	13425	40498;40499;40500	chr2:178580194;178580193;178580192	chr2:179444921;179444920;179444919
Novex-2	13492	40699;40700;40701	chr2:178580194;178580193;178580192	chr2:179444921;179444920;179444919
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: Fn3-50
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.1705
• 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
E/A	rs1449941116	-0.903	0.581	N	0.571	0.366	0.458554320643	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	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	0.4023	ambiguous	0.2713	benign	-0.581	Destabilizing	0.581	D	0.571	neutral	N	0.470723675	None	None	N
E/C	0.9499	likely_pathogenic	0.9019	pathogenic	-0.357	Destabilizing	0.993	D	0.694	prob.neutral	None	None	None	None	N
E/D	0.1057	likely_benign	0.0926	benign	-0.531	Destabilizing	0.004	N	0.172	neutral	N	0.43043853	None	None	N
E/F	0.9378	likely_pathogenic	0.8675	pathogenic	0.053	Stabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	N
E/G	0.322	likely_benign	0.228	benign	-0.863	Destabilizing	0.83	D	0.631	neutral	N	0.483334201	None	None	N
E/H	0.7944	likely_pathogenic	0.6491	pathogenic	0.335	Stabilizing	0.98	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.807	likely_pathogenic	0.6446	pathogenic	0.166	Stabilizing	0.929	D	0.744	deleterious	None	None	None	None	N
E/K	0.5937	likely_pathogenic	0.4086	ambiguous	0.203	Stabilizing	0.581	D	0.496	neutral	N	0.484348159	None	None	N
E/L	0.814	likely_pathogenic	0.6581	pathogenic	0.166	Stabilizing	0.866	D	0.727	prob.delet.	None	None	None	None	N
E/M	0.8089	likely_pathogenic	0.6606	pathogenic	0.222	Stabilizing	0.993	D	0.653	neutral	None	None	None	None	N
E/N	0.3847	ambiguous	0.2577	benign	-0.547	Destabilizing	0.764	D	0.656	neutral	None	None	None	None	N
E/P	0.9691	likely_pathogenic	0.9001	pathogenic	-0.062	Destabilizing	0.929	D	0.748	deleterious	None	None	None	None	N
E/Q	0.3924	ambiguous	0.2654	benign	-0.425	Destabilizing	0.83	D	0.612	neutral	N	0.484348159	None	None	N
E/R	0.7264	likely_pathogenic	0.5626	ambiguous	0.583	Stabilizing	0.866	D	0.729	prob.delet.	None	None	None	None	N
E/S	0.4392	ambiguous	0.2998	benign	-0.7	Destabilizing	0.48	N	0.533	neutral	None	None	None	None	N
E/T	0.5444	ambiguous	0.3668	ambiguous	-0.442	Destabilizing	0.866	D	0.658	neutral	None	None	None	None	N
E/V	0.608	likely_pathogenic	0.4212	ambiguous	-0.062	Destabilizing	0.908	D	0.709	prob.delet.	N	0.496691969	None	None	N
E/W	0.9731	likely_pathogenic	0.9441	pathogenic	0.386	Stabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	N
E/Y	0.8348	likely_pathogenic	0.7143	pathogenic	0.35	Stabilizing	0.993	D	0.701	prob.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.