TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2123	6592;6593;6594	chr2:178775497;178775496;178775495	chr2:179640224;179640223;179640222
N2AB	2123	6592;6593;6594	chr2:178775497;178775496;178775495	chr2:179640224;179640223;179640222
N2A	2123	6592;6593;6594	chr2:178775497;178775496;178775495	chr2:179640224;179640223;179640222
N2B	2077	6454;6455;6456	chr2:178775497;178775496;178775495	chr2:179640224;179640223;179640222
Novex-1	2077	6454;6455;6456	chr2:178775497;178775496;178775495	chr2:179640224;179640223;179640222
Novex-2	2077	6454;6455;6456	chr2:178775497;178775496;178775495	chr2:179640224;179640223;179640222
Novex-3	2123	6592;6593;6594	chr2:178775497;178775496;178775495	chr2:179640224;179640223;179640222

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Ig-10
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.2242
• 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/L	rs530807674	-0.264	1.0	D	0.689	0.768	0.704837425536	gnomAD-2.1.1	1.42E-05	None	None	None	None	N	None	4.01E-05	0	None	0	0	None	6.53E-05	None	0	0	1.38812E-04
R/L	rs530807674	-0.264	1.0	D	0.689	0.768	0.704837425536	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	6.22148E-04	0
R/L	rs530807674	-0.264	1.0	D	0.689	0.768	0.704837425536	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/L	rs530807674	-0.264	1.0	D	0.689	0.768	0.704837425536	gnomAD-4.0.0	8.67428E-06	None	None	None	None	N	None	1.33298E-05	0	None	0	0	None	0	0	0	1.31764E-04	1.59985E-05
R/Q	rs530807674	-0.626	1.0	D	0.693	0.611	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.84593E-04	0	None	0	0	None	9.8E-05	None	0	1.76E-05	0
R/Q	rs530807674	-0.626	1.0	D	0.693	0.611	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.93125E-04	0	0	0	0	None	0	0	0	0	0
R/Q	rs530807674	-0.626	1.0	D	0.693	0.611	None	gnomAD-4.0.0	2.2307E-05	None	None	None	None	N	None	2.80381E-04	0	None	0	6.69225E-05	None	0	0	8.47462E-06	2.19597E-05	0
R/W	rs777316854	-0.586	1.0	D	0.7	0.756	0.663099739152	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	6.15E-05	2.9E-05	None	0	5.46E-05	None	3.27E-05	None	0	3.52E-05	0
R/W	rs777316854	-0.586	1.0	D	0.7	0.756	0.663099739152	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	2.94E-05	0	0
R/W	rs777316854	-0.586	1.0	D	0.7	0.756	0.663099739152	gnomAD-4.0.0	1.17732E-05	None	None	None	None	N	None	6.67735E-05	1.66778E-05	None	0	2.23035E-05	None	0	0	7.62711E-06	2.19602E-05	1.60046E-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	0.7582	likely_pathogenic	0.7973	pathogenic	-0.782	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
R/C	0.4991	ambiguous	0.5456	ambiguous	-0.739	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
R/D	0.8159	likely_pathogenic	0.8553	pathogenic	0.015	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
R/E	0.6475	likely_pathogenic	0.6797	pathogenic	0.153	Stabilizing	0.999	D	0.581	neutral	None	None	None	None	N
R/F	0.9273	likely_pathogenic	0.9332	pathogenic	-0.576	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/G	0.6158	likely_pathogenic	0.6838	pathogenic	-1.105	Destabilizing	1.0	D	0.689	prob.neutral	D	0.619668964	None	None	N
R/H	0.1905	likely_benign	0.2111	benign	-1.372	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
R/I	0.7285	likely_pathogenic	0.7208	pathogenic	0.089	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
R/K	0.2146	likely_benign	0.2211	benign	-0.732	Destabilizing	0.998	D	0.463	neutral	None	None	None	None	N
R/L	0.6478	likely_pathogenic	0.6735	pathogenic	0.089	Stabilizing	1.0	D	0.689	prob.neutral	D	0.689467601	None	None	N
R/M	0.7491	likely_pathogenic	0.7548	pathogenic	-0.292	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
R/N	0.7319	likely_pathogenic	0.7837	pathogenic	-0.293	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/P	0.9628	likely_pathogenic	0.972	pathogenic	-0.18	Destabilizing	1.0	D	0.682	prob.neutral	D	0.632044053	None	None	N
R/Q	0.187	likely_benign	0.2043	benign	-0.408	Destabilizing	1.0	D	0.693	prob.neutral	D	0.633757835	None	None	N
R/S	0.7576	likely_pathogenic	0.8045	pathogenic	-1.071	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
R/T	0.5421	ambiguous	0.5753	pathogenic	-0.741	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
R/V	0.7669	likely_pathogenic	0.7753	pathogenic	-0.18	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
R/W	0.6434	likely_pathogenic	0.6668	pathogenic	-0.24	Destabilizing	1.0	D	0.7	prob.neutral	D	0.776595459	None	None	N
R/Y	0.7846	likely_pathogenic	0.8097	pathogenic	0.052	Stabilizing	1.0	D	0.707	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.