TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8757	26494;26495;26496	chr2:178714505;178714504;178714503	chr2:179579232;179579231;179579230
N2AB	8440	25543;25544;25545	chr2:178714505;178714504;178714503	chr2:179579232;179579231;179579230
N2A	7513	22762;22763;22764	chr2:178714505;178714504;178714503	chr2:179579232;179579231;179579230
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-73
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0923
• 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
T/A	None	None	None	N	0.3	0.116	0.0138822411134	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
T/I	rs1357129552	None	0.117	N	0.679	0.266	0.171388866994	gnomAD-4.0.0	6.84407E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99628E-07	0	0
T/N	None	None	0.211	N	0.683	0.263	0.167679373172	gnomAD-4.0.0	6.84407E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15988E-05	0
T/S	None	None	0.027	N	0.517	0.08	0.0716867268079	gnomAD-4.0.0	6.84407E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99628E-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
T/A	0.0496	likely_benign	0.0513	benign	-1.208	Destabilizing	None	N	0.3	neutral	N	0.296033171	None	None	N
T/C	0.3606	ambiguous	0.4108	ambiguous	-0.839	Destabilizing	0.001	N	0.558	neutral	None	None	None	None	N
T/D	0.7013	likely_pathogenic	0.8478	pathogenic	-1.949	Destabilizing	0.149	N	0.702	prob.neutral	None	None	None	None	N
T/E	0.6749	likely_pathogenic	0.8416	pathogenic	-1.672	Destabilizing	0.149	N	0.68	prob.neutral	None	None	None	None	N
T/F	0.5529	ambiguous	0.7619	pathogenic	-0.683	Destabilizing	0.555	D	0.792	deleterious	None	None	None	None	N
T/G	0.1519	likely_benign	0.2097	benign	-1.661	Destabilizing	0.035	N	0.702	prob.neutral	None	None	None	None	N
T/H	0.6615	likely_pathogenic	0.8113	pathogenic	-1.608	Destabilizing	0.935	D	0.805	deleterious	None	None	None	None	N
T/I	0.2624	likely_benign	0.3979	ambiguous	0.02	Stabilizing	0.117	N	0.679	prob.neutral	N	0.455648327	None	None	N
T/K	0.7021	likely_pathogenic	0.8604	pathogenic	-0.336	Destabilizing	0.149	N	0.679	prob.neutral	None	None	None	None	N
T/L	0.1612	likely_benign	0.2655	benign	0.02	Stabilizing	0.035	N	0.642	neutral	None	None	None	None	N
T/M	0.1121	likely_benign	0.1773	benign	-0.236	Destabilizing	0.555	D	0.753	deleterious	None	None	None	None	N
T/N	0.2681	likely_benign	0.4035	ambiguous	-1.31	Destabilizing	0.211	N	0.683	prob.neutral	N	0.45738191	None	None	N
T/P	0.6227	likely_pathogenic	0.7878	pathogenic	-0.361	Destabilizing	0.117	N	0.729	prob.delet.	N	0.45738191	None	None	N
T/Q	0.5801	likely_pathogenic	0.7503	pathogenic	-0.892	Destabilizing	0.555	D	0.745	deleterious	None	None	None	None	N
T/R	0.6141	likely_pathogenic	0.795	pathogenic	-0.744	Destabilizing	0.38	N	0.741	deleterious	None	None	None	None	N
T/S	0.1141	likely_benign	0.1428	benign	-1.5	Destabilizing	0.027	N	0.517	neutral	N	0.40118191	None	None	N
T/V	0.1445	likely_benign	0.1895	benign	-0.361	Destabilizing	0.035	N	0.571	neutral	None	None	None	None	N
T/W	0.9037	likely_pathogenic	0.9677	pathogenic	-0.975	Destabilizing	0.935	D	0.799	deleterious	None	None	None	None	N
T/Y	0.5908	likely_pathogenic	0.7792	pathogenic	-0.541	Destabilizing	0.555	D	0.802	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.