TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1292	4099;4100;4101	chr2:178779318;178779317;178779316	chr2:179644045;179644044;179644043
N2AB	1292	4099;4100;4101	chr2:178779318;178779317;178779316	chr2:179644045;179644044;179644043
N2A	1292	4099;4100;4101	chr2:178779318;178779317;178779316	chr2:179644045;179644044;179644043
N2B	1246	3961;3962;3963	chr2:178779318;178779317;178779316	chr2:179644045;179644044;179644043
Novex-1	1246	3961;3962;3963	chr2:178779318;178779317;178779316	chr2:179644045;179644044;179644043
Novex-2	1246	3961;3962;3963	chr2:178779318;178779317;178779316	chr2:179644045;179644044;179644043
Novex-3	1292	4099;4100;4101	chr2:178779318;178779317;178779316	chr2:179644045;179644044;179644043

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-5
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2729
• 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/V	None	None	0.89	N	0.613	0.357	0.654740151078	gnomAD-4.0.0	1.20083E-06	None	None	None	None	N	None	0	0	None	1.94401E-04	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
G/A	0.1121	likely_benign	0.1187	benign	-0.57	Destabilizing	0.006	N	0.318	neutral	N	0.452380774	None	None	N
G/C	0.2368	likely_benign	0.2395	benign	-0.998	Destabilizing	0.994	D	0.664	neutral	None	None	None	None	N
G/D	0.5487	ambiguous	0.5808	pathogenic	-0.541	Destabilizing	0.956	D	0.605	neutral	None	None	None	None	N
G/E	0.4417	ambiguous	0.4639	ambiguous	-0.656	Destabilizing	0.942	D	0.588	neutral	N	0.42430115	None	None	N
G/F	0.6739	likely_pathogenic	0.7046	pathogenic	-1.157	Destabilizing	0.978	D	0.685	prob.neutral	None	None	None	None	N
G/H	0.5422	ambiguous	0.5961	pathogenic	-0.907	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	N
G/I	0.2731	likely_benign	0.3019	benign	-0.454	Destabilizing	0.956	D	0.679	prob.neutral	None	None	None	None	N
G/K	0.6211	likely_pathogenic	0.6535	pathogenic	-0.814	Destabilizing	0.956	D	0.587	neutral	None	None	None	None	N
G/L	0.4927	ambiguous	0.5575	ambiguous	-0.454	Destabilizing	0.915	D	0.615	neutral	None	None	None	None	N
G/M	0.5204	ambiguous	0.5759	pathogenic	-0.429	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
G/N	0.4577	ambiguous	0.5118	ambiguous	-0.485	Destabilizing	0.956	D	0.625	neutral	None	None	None	None	N
G/P	0.9677	likely_pathogenic	0.9731	pathogenic	-0.455	Destabilizing	0.978	D	0.65	neutral	None	None	None	None	N
G/Q	0.4565	ambiguous	0.4974	ambiguous	-0.743	Destabilizing	0.978	D	0.654	neutral	None	None	None	None	N
G/R	0.4201	ambiguous	0.4444	ambiguous	-0.475	Destabilizing	0.97	D	0.651	neutral	N	0.408037412	None	None	N
G/S	0.0983	likely_benign	0.1069	benign	-0.778	Destabilizing	0.193	N	0.375	neutral	None	None	None	None	N
G/T	0.1509	likely_benign	0.1776	benign	-0.808	Destabilizing	0.754	D	0.564	neutral	None	None	None	None	N
G/V	0.1809	likely_benign	0.2032	benign	-0.455	Destabilizing	0.89	D	0.613	neutral	N	0.416883885	None	None	N
G/W	0.6414	likely_pathogenic	0.6619	pathogenic	-1.336	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
G/Y	0.6124	likely_pathogenic	0.6389	pathogenic	-0.948	Destabilizing	0.993	D	0.677	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.