TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1377	4354;4355;4356	chr2:178778953;178778952;178778951	chr2:179643680;179643679;179643678
N2AB	1377	4354;4355;4356	chr2:178778953;178778952;178778951	chr2:179643680;179643679;179643678
N2A	1377	4354;4355;4356	chr2:178778953;178778952;178778951	chr2:179643680;179643679;179643678
N2B	1331	4216;4217;4218	chr2:178778953;178778952;178778951	chr2:179643680;179643679;179643678
Novex-1	1331	4216;4217;4218	chr2:178778953;178778952;178778951	chr2:179643680;179643679;179643678
Novex-2	1331	4216;4217;4218	chr2:178778953;178778952;178778951	chr2:179643680;179643679;179643678
Novex-3	1377	4354;4355;4356	chr2:178778953;178778952;178778951	chr2:179643680;179643679;179643678

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-5
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.1182
• 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
G/R	rs749203945	-0.662	0.982	D	0.752	0.466	0.772884586864	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.62E-05	0	0
G/R	rs749203945	-0.662	0.982	D	0.752	0.466	0.772884586864	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88225E-05	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
G/A	0.2277	likely_benign	0.2071	benign	-0.461	Destabilizing	0.02	N	0.286	neutral	N	0.388945693	None	None	N
G/C	0.8199	likely_pathogenic	0.8113	pathogenic	-0.88	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
G/D	0.9962	likely_pathogenic	0.9959	pathogenic	-0.924	Destabilizing	0.986	D	0.73	prob.delet.	None	None	None	None	N
G/E	0.9951	likely_pathogenic	0.9952	pathogenic	-0.851	Destabilizing	0.982	D	0.742	deleterious	D	0.638947456	None	None	N
G/F	0.9945	likely_pathogenic	0.9938	pathogenic	-0.618	Destabilizing	0.993	D	0.798	deleterious	None	None	None	None	N
G/H	0.9972	likely_pathogenic	0.9973	pathogenic	-1.439	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
G/I	0.9725	likely_pathogenic	0.9707	pathogenic	0.371	Stabilizing	0.986	D	0.791	deleterious	None	None	None	None	N
G/K	0.9983	likely_pathogenic	0.9984	pathogenic	-0.809	Destabilizing	0.986	D	0.739	prob.delet.	None	None	None	None	N
G/L	0.9775	likely_pathogenic	0.976	pathogenic	0.371	Stabilizing	0.986	D	0.781	deleterious	None	None	None	None	N
G/M	0.9836	likely_pathogenic	0.9827	pathogenic	0.109	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
G/N	0.9918	likely_pathogenic	0.9923	pathogenic	-0.763	Destabilizing	0.986	D	0.641	neutral	None	None	None	None	N
G/P	0.9996	likely_pathogenic	0.9996	pathogenic	0.14	Stabilizing	0.993	D	0.76	deleterious	None	None	None	None	N
G/Q	0.9913	likely_pathogenic	0.9922	pathogenic	-0.7	Destabilizing	0.993	D	0.729	prob.delet.	None	None	None	None	N
G/R	0.9918	likely_pathogenic	0.9928	pathogenic	-0.9	Destabilizing	0.982	D	0.752	deleterious	D	0.598217075	None	None	N
G/S	0.5127	ambiguous	0.5183	ambiguous	-1.178	Destabilizing	0.214	N	0.385	neutral	None	None	None	None	N
G/T	0.8807	likely_pathogenic	0.8558	pathogenic	-0.977	Destabilizing	0.91	D	0.727	prob.delet.	None	None	None	None	N
G/V	0.9173	likely_pathogenic	0.9106	pathogenic	0.14	Stabilizing	0.964	D	0.781	deleterious	N	0.484016625	None	None	N
G/W	0.9959	likely_pathogenic	0.9959	pathogenic	-1.22	Destabilizing	0.999	D	0.735	prob.delet.	D	0.599530629	None	None	N
G/Y	0.9964	likely_pathogenic	0.9962	pathogenic	-0.628	Destabilizing	0.999	D	0.799	deleterious	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.