TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35136	105631;105632;105633	chr2:178531209;178531208;178531207	chr2:179395936;179395935;179395934
N2AB	33495	100708;100709;100710	chr2:178531209;178531208;178531207	chr2:179395936;179395935;179395934
N2A	32568	97927;97928;97929	chr2:178531209;178531208;178531207	chr2:179395936;179395935;179395934
N2B	26071	78436;78437;78438	chr2:178531209;178531208;178531207	chr2:179395936;179395935;179395934
Novex-1	26196	78811;78812;78813	chr2:178531209;178531208;178531207	chr2:179395936;179395935;179395934
Novex-2	26263	79012;79013;79014	chr2:178531209;178531208;178531207	chr2:179395936;179395935;179395934
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Ig-164
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7321
• 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/G	rs372875128	-0.091	0.911	N	0.476	0.353	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.65344E-04	0	None	0	0	None	0	None	0	0	0
R/G	rs372875128	-0.091	0.911	N	0.476	0.353	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20639E-04	0	0	0	0	None	0	0	0	0	0
R/G	rs372875128	-0.091	0.911	N	0.476	0.353	None	gnomAD-4.0.0	3.71781E-06	None	None	None	None	N	None	8.00833E-05	0	None	0	0	None	0	0	0	0	0
R/Q	rs554213990	0.196	0.113	N	0.129	0.165	0.218845423259	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	3.27E-05	None	0	1.77E-05	0
R/Q	rs554213990	0.196	0.113	N	0.129	0.165	0.218845423259	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	3.16456E-03	1.47E-05	0	0
R/Q	rs554213990	0.196	0.113	N	0.129	0.165	0.218845423259	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/Q	rs554213990	0.196	0.113	N	0.129	0.165	0.218845423259	gnomAD-4.0.0	1.92081E-05	None	None	None	None	N	None	2.6661E-05	0	None	3.37747E-05	0	None	0	1.64962E-04	1.61036E-05	5.49064E-05	4.80077E-05
R/W	rs372875128	-0.335	0.999	N	0.491	0.55	0.559195274915	gnomAD-2.1.1	4.99E-05	None	None	None	None	N	None	0	0	None	0	6.14251E-04	None	0	None	0	1.56E-05	0
R/W	rs372875128	-0.335	0.999	N	0.491	0.55	0.559195274915	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	1.92382E-04	None	0	0	2.94E-05	0	0
R/W	rs372875128	-0.335	0.999	N	0.491	0.55	0.559195274915	gnomAD-4.0.0	4.27548E-05	None	None	None	None	N	None	0	0	None	0	6.23636E-04	None	0	0	3.2207E-05	0	4.80292E-05

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	0.4757	ambiguous	0.4398	ambiguous	0.042	Stabilizing	0.688	D	0.438	neutral	None	None	None	None	N
R/C	0.2736	likely_benign	0.2334	benign	-0.212	Destabilizing	0.998	D	0.47	neutral	None	None	None	None	N
R/D	0.7971	likely_pathogenic	0.7669	pathogenic	-0.284	Destabilizing	0.842	D	0.488	neutral	None	None	None	None	N
R/E	0.4728	ambiguous	0.437	ambiguous	-0.247	Destabilizing	0.525	D	0.443	neutral	None	None	None	None	N
R/F	0.6831	likely_pathogenic	0.647	pathogenic	-0.289	Destabilizing	0.991	D	0.472	neutral	None	None	None	None	N
R/G	0.3416	ambiguous	0.3146	benign	-0.089	Destabilizing	0.911	D	0.476	neutral	N	0.489692769	None	None	N
R/H	0.1386	likely_benign	0.1265	benign	-0.591	Destabilizing	0.974	D	0.479	neutral	None	None	None	None	N
R/I	0.4227	ambiguous	0.3909	ambiguous	0.34	Stabilizing	0.974	D	0.485	neutral	None	None	None	None	N
R/K	0.1423	likely_benign	0.1318	benign	-0.132	Destabilizing	0.525	D	0.404	neutral	None	None	None	None	N
R/L	0.3351	likely_benign	0.3025	benign	0.34	Stabilizing	0.911	D	0.476	neutral	N	0.494175869	None	None	N
R/M	0.4768	ambiguous	0.4288	ambiguous	-0.076	Destabilizing	0.991	D	0.471	neutral	None	None	None	None	N
R/N	0.7018	likely_pathogenic	0.6634	pathogenic	-0.024	Destabilizing	0.842	D	0.471	neutral	None	None	None	None	N
R/P	0.6708	likely_pathogenic	0.6495	pathogenic	0.258	Stabilizing	0.986	D	0.458	neutral	N	0.491212922	None	None	N
R/Q	0.1169	likely_benign	0.1112	benign	-0.067	Destabilizing	0.113	N	0.129	neutral	N	0.429046955	None	None	N
R/S	0.5416	ambiguous	0.5043	ambiguous	-0.201	Destabilizing	0.842	D	0.457	neutral	None	None	None	None	N
R/T	0.3817	ambiguous	0.3389	benign	-0.063	Destabilizing	0.842	D	0.456	neutral	None	None	None	None	N
R/V	0.4555	ambiguous	0.4196	ambiguous	0.258	Stabilizing	0.974	D	0.453	neutral	None	None	None	None	N
R/W	0.2738	likely_benign	0.2462	benign	-0.481	Destabilizing	0.999	D	0.491	neutral	N	0.505370882	None	None	N
R/Y	0.5244	ambiguous	0.4813	ambiguous	-0.075	Destabilizing	0.991	D	0.496	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.