TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2975	9148;9149;9150	chr2:178768913;178768912;178768911	chr2:179633640;179633639;179633638
N2AB	2975	9148;9149;9150	chr2:178768913;178768912;178768911	chr2:179633640;179633639;179633638
N2A	2975	9148;9149;9150	chr2:178768913;178768912;178768911	chr2:179633640;179633639;179633638
N2B	2929	9010;9011;9012	chr2:178768913;178768912;178768911	chr2:179633640;179633639;179633638
Novex-1	2929	9010;9011;9012	chr2:178768913;178768912;178768911	chr2:179633640;179633639;179633638
Novex-2	2929	9010;9011;9012	chr2:178768913;178768912;178768911	chr2:179633640;179633639;179633638
Novex-3	2975	9148;9149;9150	chr2:178768913;178768912;178768911	chr2:179633640;179633639;179633638

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-20
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1159
• 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
L/M	rs1445649834	-1.114	0.981	N	0.482	0.259	0.396044805602	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.63E-05	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
L/A	0.9808	likely_pathogenic	0.9797	pathogenic	-2.274	Highly Destabilizing	0.997	D	0.628	neutral	None	None	None	None	N
L/C	0.9901	likely_pathogenic	0.9904	pathogenic	-1.751	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-1.882	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/E	0.9981	likely_pathogenic	0.9978	pathogenic	-1.701	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.9749	likely_pathogenic	0.9736	pathogenic	-1.336	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
L/G	0.9967	likely_pathogenic	0.9958	pathogenic	-2.785	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/H	0.998	likely_pathogenic	0.9979	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/I	0.7054	likely_pathogenic	0.7398	pathogenic	-0.834	Destabilizing	0.994	D	0.492	neutral	None	None	None	None	N
L/K	0.9966	likely_pathogenic	0.9966	pathogenic	-1.569	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/M	0.7244	likely_pathogenic	0.7387	pathogenic	-0.907	Destabilizing	0.981	D	0.482	neutral	N	0.460403147	None	None	N
L/N	0.9979	likely_pathogenic	0.9977	pathogenic	-1.744	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/P	0.9688	likely_pathogenic	0.9522	pathogenic	-1.29	Destabilizing	1.0	D	0.906	deleterious	N	0.441355638	None	None	N
L/Q	0.9946	likely_pathogenic	0.9941	pathogenic	-1.666	Destabilizing	0.999	D	0.887	deleterious	D	0.608812611	None	None	N
L/R	0.9946	likely_pathogenic	0.9941	pathogenic	-1.283	Destabilizing	0.999	D	0.872	deleterious	D	0.608812611	None	None	N
L/S	0.9984	likely_pathogenic	0.9981	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/T	0.9906	likely_pathogenic	0.9902	pathogenic	-2.221	Highly Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
L/V	0.8209	likely_pathogenic	0.8323	pathogenic	-1.29	Destabilizing	0.992	D	0.482	neutral	D	0.567279713	None	None	N
L/W	0.9974	likely_pathogenic	0.9972	pathogenic	-1.565	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/Y	0.9985	likely_pathogenic	0.9985	pathogenic	-1.288	Destabilizing	1.0	D	0.857	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.