TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13733	41422;41423;41424	chr2:178636530;178636529;178636528	chr2:179501257;179501256;179501255
N2AB	12092	36499;36500;36501	chr2:178636530;178636529;178636528	chr2:179501257;179501256;179501255
N2A	11165	33718;33719;33720	chr2:178636530;178636529;178636528	chr2:179501257;179501256;179501255
N2B	4668	14227;14228;14229	chr2:178636530;178636529;178636528	chr2:179501257;179501256;179501255
Novex-1	4793	14602;14603;14604	chr2:178636530;178636529;178636528	chr2:179501257;179501256;179501255
Novex-2	4860	14803;14804;14805	chr2:178636530;178636529;178636528	chr2:179501257;179501256;179501255
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-87
• Domain position: 50
• Structural Position: 122
• Q(SASA): 0.2717
• 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
R/K	rs1026532541	None	0.002	N	0.104	0.097	0.259761712551	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
R/K	rs1026532541	None	0.002	N	0.104	0.097	0.259761712551	gnomAD-4.0.0	1.31572E-05	None	None	None	None	N	None	4.82789E-05	0	None	0	0	None	0	0	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
R/A	0.9452	likely_pathogenic	0.9619	pathogenic	-0.67	Destabilizing	0.688	D	0.394	neutral	None	None	None	None	N
R/C	0.764	likely_pathogenic	0.7902	pathogenic	-0.563	Destabilizing	0.998	D	0.452	neutral	None	None	None	None	N
R/D	0.9846	likely_pathogenic	0.9879	pathogenic	0.061	Stabilizing	0.842	D	0.466	neutral	None	None	None	None	N
R/E	0.895	likely_pathogenic	0.9201	pathogenic	0.212	Stabilizing	0.525	D	0.388	neutral	None	None	None	None	N
R/F	0.9682	likely_pathogenic	0.9752	pathogenic	-0.403	Destabilizing	0.991	D	0.479	neutral	None	None	None	None	N
R/G	0.9286	likely_pathogenic	0.9411	pathogenic	-1.001	Destabilizing	0.801	D	0.463	neutral	N	0.50724639	None	None	N
R/H	0.3357	likely_benign	0.3998	ambiguous	-1.403	Destabilizing	0.991	D	0.461	neutral	None	None	None	None	N
R/I	0.8165	likely_pathogenic	0.8328	pathogenic	0.225	Stabilizing	0.974	D	0.487	neutral	None	None	None	None	N
R/K	0.2761	likely_benign	0.3091	benign	-0.496	Destabilizing	0.002	N	0.104	neutral	N	0.480680471	None	None	N
R/L	0.7801	likely_pathogenic	0.8181	pathogenic	0.225	Stabilizing	0.842	D	0.463	neutral	None	None	None	None	N
R/M	0.8883	likely_pathogenic	0.9063	pathogenic	-0.228	Destabilizing	0.989	D	0.479	neutral	D	0.591736491	None	None	N
R/N	0.9562	likely_pathogenic	0.9692	pathogenic	-0.133	Destabilizing	0.842	D	0.41	neutral	None	None	None	None	N
R/P	0.9956	likely_pathogenic	0.9971	pathogenic	-0.052	Destabilizing	0.915	D	0.481	neutral	None	None	None	None	N
R/Q	0.3513	ambiguous	0.415	ambiguous	-0.195	Destabilizing	0.842	D	0.423	neutral	None	None	None	None	N
R/S	0.9479	likely_pathogenic	0.9597	pathogenic	-0.852	Destabilizing	0.625	D	0.445	neutral	N	0.498006338	None	None	N
R/T	0.8496	likely_pathogenic	0.8841	pathogenic	-0.5	Destabilizing	0.801	D	0.47	neutral	N	0.512448086	None	None	N
R/V	0.8516	likely_pathogenic	0.8862	pathogenic	-0.052	Destabilizing	0.915	D	0.492	neutral	None	None	None	None	N
R/W	0.8002	likely_pathogenic	0.8065	pathogenic	-0.111	Destabilizing	0.997	D	0.485	neutral	D	0.593302614	None	None	N
R/Y	0.9012	likely_pathogenic	0.9209	pathogenic	0.177	Stabilizing	0.991	D	0.482	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.