TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7161	21706;21707;21708	chr2:178723619;178723618;178723617	chr2:179588346;179588345;179588344
N2AB	6844	20755;20756;20757	chr2:178723619;178723618;178723617	chr2:179588346;179588345;179588344
N2A	5917	17974;17975;17976	chr2:178723619;178723618;178723617	chr2:179588346;179588345;179588344
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-56
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5058
• 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	rs1225806135	-0.034	0.002	N	0.087	0.159	0.15556083564	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
R/K	rs1225806135	-0.034	0.002	N	0.087	0.159	0.15556083564	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
R/K	rs1225806135	-0.034	0.002	N	0.087	0.159	0.15556083564	gnomAD-4.0.0	3.84877E-06	None	None	None	None	N	None	1.69302E-05	1.69877E-05	None	0	0	None	0	0	2.39526E-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
R/A	0.2034	likely_benign	0.1861	benign	-0.116	Destabilizing	0.176	N	0.191	neutral	None	None	None	None	N
R/C	0.168	likely_benign	0.1735	benign	-0.371	Destabilizing	0.017	N	0.229	neutral	None	None	None	None	N
R/D	0.5282	ambiguous	0.493	ambiguous	-0.07	Destabilizing	0.704	D	0.303	neutral	None	None	None	None	N
R/E	0.2069	likely_benign	0.1935	benign	-0.021	Destabilizing	0.329	N	0.213	neutral	None	None	None	None	N
R/F	0.436	ambiguous	0.422	ambiguous	-0.433	Destabilizing	0.981	D	0.233	neutral	None	None	None	None	N
R/G	0.1417	likely_benign	0.1326	benign	-0.274	Destabilizing	0.425	N	0.24	neutral	N	0.512433556	None	None	N
R/H	0.0984	likely_benign	0.0979	benign	-0.668	Destabilizing	0.944	D	0.325	neutral	None	None	None	None	N
R/I	0.2021	likely_benign	0.1967	benign	0.257	Stabilizing	0.642	D	0.307	neutral	N	0.513356276	None	None	N
R/K	0.0732	likely_benign	0.0707	benign	-0.19	Destabilizing	0.002	N	0.087	neutral	N	0.42908424	None	None	N
R/L	0.1826	likely_benign	0.1702	benign	0.257	Stabilizing	0.495	N	0.235	neutral	None	None	None	None	N
R/M	0.1656	likely_benign	0.1657	benign	-0.109	Destabilizing	0.981	D	0.256	neutral	None	None	None	None	N
R/N	0.3945	ambiguous	0.3635	ambiguous	-0.044	Destabilizing	0.704	D	0.192	neutral	None	None	None	None	N
R/P	0.8488	likely_pathogenic	0.8264	pathogenic	0.152	Stabilizing	0.828	D	0.309	neutral	None	None	None	None	N
R/Q	0.084	likely_benign	0.0817	benign	-0.144	Destabilizing	0.085	N	0.14	neutral	None	None	None	None	N
R/S	0.2449	likely_benign	0.2257	benign	-0.411	Destabilizing	0.065	N	0.155	neutral	N	0.444013621	None	None	N
R/T	0.1121	likely_benign	0.1089	benign	-0.24	Destabilizing	0.023	N	0.157	neutral	N	0.450286232	None	None	N
R/V	0.2586	likely_benign	0.2434	benign	0.152	Stabilizing	0.704	D	0.284	neutral	None	None	None	None	N
R/W	0.1412	likely_benign	0.1494	benign	-0.513	Destabilizing	0.995	D	0.206	neutral	None	None	None	None	N
R/Y	0.3177	likely_benign	0.3083	benign	-0.099	Destabilizing	0.981	D	0.241	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.