TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31776	95551;95552;95553	chr2:178545910;178545909;178545908	chr2:179410637;179410636;179410635
N2AB	30135	90628;90629;90630	chr2:178545910;178545909;178545908	chr2:179410637;179410636;179410635
N2A	29208	87847;87848;87849	chr2:178545910;178545909;178545908	chr2:179410637;179410636;179410635
N2B	22711	68356;68357;68358	chr2:178545910;178545909;178545908	chr2:179410637;179410636;179410635
Novex-1	22836	68731;68732;68733	chr2:178545910;178545909;178545908	chr2:179410637;179410636;179410635
Novex-2	22903	68932;68933;68934	chr2:178545910;178545909;178545908	chr2:179410637;179410636;179410635
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-119
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.2398
• 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
N/S	rs1696881072	None	0.999	N	0.517	0.397	0.163833314356	gnomAD-4.0.0	1.36838E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79893E-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
N/A	0.7431	likely_pathogenic	0.7616	pathogenic	-0.938	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
N/C	0.5955	likely_pathogenic	0.6293	pathogenic	-0.075	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
N/D	0.7423	likely_pathogenic	0.7507	pathogenic	-0.824	Destabilizing	0.999	D	0.585	neutral	N	0.507399484	None	None	N
N/E	0.9248	likely_pathogenic	0.935	pathogenic	-0.697	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
N/F	0.9609	likely_pathogenic	0.9648	pathogenic	-0.551	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
N/G	0.7224	likely_pathogenic	0.743	pathogenic	-1.309	Destabilizing	0.999	D	0.493	neutral	None	None	None	None	N
N/H	0.305	likely_benign	0.3609	ambiguous	-0.987	Destabilizing	1.0	D	0.682	prob.neutral	N	0.4798272	None	None	N
N/I	0.8538	likely_pathogenic	0.8763	pathogenic	0.022	Stabilizing	1.0	D	0.663	neutral	N	0.486826467	None	None	N
N/K	0.8957	likely_pathogenic	0.9206	pathogenic	-0.411	Destabilizing	1.0	D	0.711	prob.delet.	N	0.46730062	None	None	N
N/L	0.7673	likely_pathogenic	0.8276	pathogenic	0.022	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
N/M	0.841	likely_pathogenic	0.8647	pathogenic	0.432	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
N/P	0.9822	likely_pathogenic	0.9842	pathogenic	-0.268	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
N/Q	0.8015	likely_pathogenic	0.835	pathogenic	-0.969	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
N/R	0.838	likely_pathogenic	0.8807	pathogenic	-0.479	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
N/S	0.2069	likely_benign	0.203	benign	-1.077	Destabilizing	0.999	D	0.517	neutral	N	0.485462306	None	None	N
N/T	0.5657	likely_pathogenic	0.581	pathogenic	-0.757	Destabilizing	0.999	D	0.689	prob.neutral	N	0.445263548	None	None	N
N/V	0.803	likely_pathogenic	0.8256	pathogenic	-0.268	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
N/W	0.9806	likely_pathogenic	0.9842	pathogenic	-0.324	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
N/Y	0.6829	likely_pathogenic	0.7316	pathogenic	-0.113	Destabilizing	1.0	D	0.651	neutral	N	0.507906463	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.