TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2899	8920;8921;8922	chr2:178769886;178769885;178769884	chr2:179634613;179634612;179634611
N2AB	2899	8920;8921;8922	chr2:178769886;178769885;178769884	chr2:179634613;179634612;179634611
N2A	2899	8920;8921;8922	chr2:178769886;178769885;178769884	chr2:179634613;179634612;179634611
N2B	2853	8782;8783;8784	chr2:178769886;178769885;178769884	chr2:179634613;179634612;179634611
Novex-1	2853	8782;8783;8784	chr2:178769886;178769885;178769884	chr2:179634613;179634612;179634611
Novex-2	2853	8782;8783;8784	chr2:178769886;178769885;178769884	chr2:179634613;179634612;179634611
Novex-3	2899	8920;8921;8922	chr2:178769886;178769885;178769884	chr2:179634613;179634612;179634611

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-19
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1148
• 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
A/S	rs1561217531	None	1.0	D	0.599	0.565	0.530109961917	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
A/S	rs1561217531	None	1.0	D	0.599	0.565	0.530109961917	gnomAD-4.0.0	1.59053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85652E-06	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
A/C	0.7513	likely_pathogenic	0.8197	pathogenic	-0.861	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
A/D	0.9875	likely_pathogenic	0.9952	pathogenic	-0.703	Destabilizing	1.0	D	0.847	deleterious	D	0.727881516	None	None	N
A/E	0.9748	likely_pathogenic	0.9899	pathogenic	-0.618	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
A/F	0.9206	likely_pathogenic	0.9619	pathogenic	-0.625	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/G	0.5398	ambiguous	0.5901	pathogenic	-1.139	Destabilizing	1.0	D	0.581	neutral	D	0.705188949	None	None	N
A/H	0.9842	likely_pathogenic	0.9936	pathogenic	-1.267	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/I	0.5875	likely_pathogenic	0.72	pathogenic	0.173	Stabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/K	0.9893	likely_pathogenic	0.9962	pathogenic	-0.882	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/L	0.6457	likely_pathogenic	0.7564	pathogenic	0.173	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
A/M	0.7442	likely_pathogenic	0.8485	pathogenic	-0.029	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/N	0.9689	likely_pathogenic	0.9857	pathogenic	-0.843	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/P	0.9837	likely_pathogenic	0.9903	pathogenic	-0.092	Destabilizing	1.0	D	0.865	deleterious	D	0.764438869	None	None	N
A/Q	0.9608	likely_pathogenic	0.9825	pathogenic	-0.774	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
A/R	0.9739	likely_pathogenic	0.9887	pathogenic	-0.834	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/S	0.348	ambiguous	0.4202	ambiguous	-1.368	Destabilizing	1.0	D	0.599	neutral	D	0.689355677	None	None	N
A/T	0.2954	likely_benign	0.4071	ambiguous	-1.138	Destabilizing	1.0	D	0.728	prob.delet.	D	0.665696958	None	None	N
A/V	0.2627	likely_benign	0.3667	ambiguous	-0.092	Destabilizing	1.0	D	0.637	neutral	N	0.514386981	None	None	N
A/W	0.996	likely_pathogenic	0.9985	pathogenic	-1.095	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/Y	0.9762	likely_pathogenic	0.9897	pathogenic	-0.577	Destabilizing	1.0	D	0.871	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.