TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2785	8578;8579;8580	chr2:178770439;178770438;178770437	chr2:179635166;179635165;179635164
N2AB	2785	8578;8579;8580	chr2:178770439;178770438;178770437	chr2:179635166;179635165;179635164
N2A	2785	8578;8579;8580	chr2:178770439;178770438;178770437	chr2:179635166;179635165;179635164
N2B	2739	8440;8441;8442	chr2:178770439;178770438;178770437	chr2:179635166;179635165;179635164
Novex-1	2739	8440;8441;8442	chr2:178770439;178770438;178770437	chr2:179635166;179635165;179635164
Novex-2	2739	8440;8441;8442	chr2:178770439;178770438;178770437	chr2:179635166;179635165;179635164
Novex-3	2785	8578;8579;8580	chr2:178770439;178770438;178770437	chr2:179635166;179635165;179635164

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-17
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.4824
• 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	None	None	0.984	D	0.679	0.583	0.817025628476	gnomAD-4.0.0	1.59056E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.1115	likely_benign	0.1376	benign	-0.21	Destabilizing	0.64	D	0.401	neutral	D	0.550115696	None	None	N
G/C	0.2732	likely_benign	0.3669	ambiguous	-0.786	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
G/D	0.4523	ambiguous	0.6465	pathogenic	-0.063	Destabilizing	0.919	D	0.571	neutral	None	None	None	None	N
G/E	0.3303	likely_benign	0.5299	ambiguous	-0.136	Destabilizing	0.968	D	0.637	neutral	D	0.547950279	None	None	N
G/F	0.5234	ambiguous	0.6595	pathogenic	-0.609	Destabilizing	0.988	D	0.737	prob.delet.	None	None	None	None	N
G/H	0.4768	ambiguous	0.624	pathogenic	-0.464	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
G/I	0.2591	likely_benign	0.3669	ambiguous	-0.022	Destabilizing	0.976	D	0.736	prob.delet.	None	None	None	None	N
G/K	0.599	likely_pathogenic	0.7732	pathogenic	-0.635	Destabilizing	0.976	D	0.633	neutral	None	None	None	None	N
G/L	0.3887	ambiguous	0.5343	ambiguous	-0.022	Destabilizing	0.952	D	0.678	prob.neutral	None	None	None	None	N
G/M	0.4319	ambiguous	0.5425	ambiguous	-0.381	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
G/N	0.358	ambiguous	0.4661	ambiguous	-0.423	Destabilizing	0.919	D	0.483	neutral	None	None	None	None	N
G/P	0.8926	likely_pathogenic	0.9568	pathogenic	-0.047	Destabilizing	0.988	D	0.677	prob.neutral	None	None	None	None	N
G/Q	0.42	ambiguous	0.5644	pathogenic	-0.521	Destabilizing	0.988	D	0.687	prob.neutral	None	None	None	None	N
G/R	0.448	ambiguous	0.6402	pathogenic	-0.406	Destabilizing	0.984	D	0.679	prob.neutral	D	0.547820448	None	None	N
G/S	0.1036	likely_benign	0.1164	benign	-0.706	Destabilizing	0.157	N	0.211	neutral	None	None	None	None	N
G/T	0.1455	likely_benign	0.1808	benign	-0.669	Destabilizing	0.132	N	0.421	neutral	None	None	None	None	N
G/V	0.1805	likely_benign	0.2576	benign	-0.047	Destabilizing	0.938	D	0.683	prob.neutral	D	0.548659177	None	None	N
G/W	0.4412	ambiguous	0.6098	pathogenic	-0.887	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
G/Y	0.454	ambiguous	0.6254	pathogenic	-0.452	Destabilizing	0.996	D	0.734	prob.delet.	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.