TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26106	78541;78542;78543	chr2:178567816;178567815;178567814	chr2:179432543;179432542;179432541
N2AB	24465	73618;73619;73620	chr2:178567816;178567815;178567814	chr2:179432543;179432542;179432541
N2A	23538	70837;70838;70839	chr2:178567816;178567815;178567814	chr2:179432543;179432542;179432541
N2B	17041	51346;51347;51348	chr2:178567816;178567815;178567814	chr2:179432543;179432542;179432541
Novex-1	17166	51721;51722;51723	chr2:178567816;178567815;178567814	chr2:179432543;179432542;179432541
Novex-2	17233	51922;51923;51924	chr2:178567816;178567815;178567814	chr2:179432543;179432542;179432541
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: Fn3-78
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1933
• 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/I	rs1706489546	None	0.852	N	0.463	0.282	0.460352466543	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1706489546	None	0.852	N	0.463	0.282	0.460352466543	gnomAD-4.0.0	5.07504E-06	None	None	None	None	N	None	1.74734E-05	0	None	0	0	None	0	0	4.81985E-06	0	0
T/S	rs768440075	-1.432	0.92	N	0.499	0.193	0.223847106136	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	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	0.1277	likely_benign	0.1269	benign	-0.976	Destabilizing	0.826	D	0.447	neutral	N	0.521868611	None	None	N
T/C	0.42	ambiguous	0.4226	ambiguous	-0.875	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	N
T/D	0.6039	likely_pathogenic	0.5826	pathogenic	-1.63	Destabilizing	0.969	D	0.524	neutral	None	None	None	None	N
T/E	0.482	ambiguous	0.4561	ambiguous	-1.473	Destabilizing	0.939	D	0.468	neutral	None	None	None	None	N
T/F	0.3178	likely_benign	0.3054	benign	-0.494	Destabilizing	0.991	D	0.611	neutral	None	None	None	None	N
T/G	0.4481	ambiguous	0.4306	ambiguous	-1.363	Destabilizing	0.969	D	0.509	neutral	None	None	None	None	N
T/H	0.3032	likely_benign	0.3028	benign	-1.563	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
T/I	0.1642	likely_benign	0.1669	benign	0.023	Stabilizing	0.852	D	0.463	neutral	N	0.482626639	None	None	N
T/K	0.2969	likely_benign	0.3077	benign	-0.941	Destabilizing	0.079	N	0.259	neutral	None	None	None	None	N
T/L	0.1279	likely_benign	0.1283	benign	0.023	Stabilizing	0.759	D	0.449	neutral	None	None	None	None	N
T/M	0.1027	likely_benign	0.1022	benign	-0.022	Destabilizing	0.991	D	0.576	neutral	None	None	None	None	N
T/N	0.1867	likely_benign	0.1879	benign	-1.449	Destabilizing	0.959	D	0.517	neutral	N	0.47867662	None	None	N
T/P	0.7133	likely_pathogenic	0.7135	pathogenic	-0.278	Destabilizing	0.996	D	0.565	neutral	N	0.519684523	None	None	N
T/Q	0.2916	likely_benign	0.2917	benign	-1.285	Destabilizing	0.982	D	0.563	neutral	None	None	None	None	N
T/R	0.2583	likely_benign	0.2585	benign	-1.033	Destabilizing	0.884	D	0.494	neutral	None	None	None	None	N
T/S	0.1311	likely_benign	0.1239	benign	-1.578	Destabilizing	0.92	D	0.499	neutral	N	0.479539199	None	None	N
T/V	0.1429	likely_benign	0.1447	benign	-0.278	Destabilizing	0.17	N	0.239	neutral	None	None	None	None	N
T/W	0.6945	likely_pathogenic	0.6872	pathogenic	-0.692	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
T/Y	0.3494	ambiguous	0.3445	ambiguous	-0.351	Destabilizing	0.997	D	0.613	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.