TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29935	90028;90029;90030	chr2:178553097;178553096;178553095	chr2:179417824;179417823;179417822
N2AB	28294	85105;85106;85107	chr2:178553097;178553096;178553095	chr2:179417824;179417823;179417822
N2A	27367	82324;82325;82326	chr2:178553097;178553096;178553095	chr2:179417824;179417823;179417822
N2B	20870	62833;62834;62835	chr2:178553097;178553096;178553095	chr2:179417824;179417823;179417822
Novex-1	20995	63208;63209;63210	chr2:178553097;178553096;178553095	chr2:179417824;179417823;179417822
Novex-2	21062	63409;63410;63411	chr2:178553097;178553096;178553095	chr2:179417824;179417823;179417822
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-106
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1732
• 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/D	rs1247896491	-2.014	0.896	N	0.625	0.275	0.346544149963	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
A/D	rs1247896491	-2.014	0.896	N	0.625	0.275	0.346544149963	gnomAD-4.0.0	1.59765E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8731E-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
A/C	0.6602	likely_pathogenic	0.6537	pathogenic	-1.142	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
A/D	0.4927	ambiguous	0.5227	ambiguous	-1.703	Destabilizing	0.896	D	0.625	neutral	N	0.432414468	None	None	N
A/E	0.5476	ambiguous	0.565	pathogenic	-1.778	Destabilizing	0.919	D	0.635	neutral	None	None	None	None	N
A/F	0.6414	likely_pathogenic	0.6379	pathogenic	-1.295	Destabilizing	0.996	D	0.674	neutral	None	None	None	None	N
A/G	0.1188	likely_benign	0.116	benign	-1.145	Destabilizing	0.026	N	0.259	neutral	N	0.302370071	None	None	N
A/H	0.7287	likely_pathogenic	0.7259	pathogenic	-1.152	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
A/I	0.7104	likely_pathogenic	0.7138	pathogenic	-0.621	Destabilizing	0.988	D	0.678	prob.neutral	None	None	None	None	N
A/K	0.822	likely_pathogenic	0.8241	pathogenic	-1.131	Destabilizing	0.919	D	0.637	neutral	None	None	None	None	N
A/L	0.3596	ambiguous	0.3824	ambiguous	-0.621	Destabilizing	0.919	D	0.633	neutral	None	None	None	None	N
A/M	0.4451	ambiguous	0.4503	ambiguous	-0.528	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
A/N	0.5028	ambiguous	0.5185	ambiguous	-0.922	Destabilizing	0.976	D	0.635	neutral	None	None	None	None	N
A/P	0.866	likely_pathogenic	0.8774	pathogenic	-0.698	Destabilizing	0.984	D	0.67	neutral	N	0.51451299	None	None	N
A/Q	0.6002	likely_pathogenic	0.6044	pathogenic	-1.224	Destabilizing	0.988	D	0.701	prob.neutral	None	None	None	None	N
A/R	0.758	likely_pathogenic	0.7625	pathogenic	-0.676	Destabilizing	0.976	D	0.677	prob.neutral	None	None	None	None	N
A/S	0.087	likely_benign	0.0889	benign	-1.172	Destabilizing	0.046	N	0.26	neutral	N	0.366688122	None	None	N
A/T	0.1843	likely_benign	0.1902	benign	-1.174	Destabilizing	0.811	D	0.603	neutral	N	0.484979517	None	None	N
A/V	0.4004	ambiguous	0.4078	ambiguous	-0.698	Destabilizing	0.896	D	0.649	neutral	N	0.515379782	None	None	N
A/W	0.9186	likely_pathogenic	0.9191	pathogenic	-1.507	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
A/Y	0.7394	likely_pathogenic	0.7303	pathogenic	-1.138	Destabilizing	0.996	D	0.679	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.