TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16029	48310;48311;48312	chr2:178616804;178616803;178616802	chr2:179481531;179481530;179481529
N2AB	14388	43387;43388;43389	chr2:178616804;178616803;178616802	chr2:179481531;179481530;179481529
N2A	13461	40606;40607;40608	chr2:178616804;178616803;178616802	chr2:179481531;179481530;179481529
N2B	6964	21115;21116;21117	chr2:178616804;178616803;178616802	chr2:179481531;179481530;179481529
Novex-1	7089	21490;21491;21492	chr2:178616804;178616803;178616802	chr2:179481531;179481530;179481529
Novex-2	7156	21691;21692;21693	chr2:178616804;178616803;178616802	chr2:179481531;179481530;179481529
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-109
• Domain position: 62
• Structural Position: 149
• Q(SASA): 0.1806
• 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
D/Y	None	None	1.0	D	0.841	0.75	0.90494787378	gnomAD-4.0.0	1.5933E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86225E-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
D/A	0.9721	likely_pathogenic	0.9752	pathogenic	0.317	Stabilizing	1.0	D	0.828	deleterious	D	0.677041626	None	None	N
D/C	0.9848	likely_pathogenic	0.9873	pathogenic	0.444	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
D/E	0.8813	likely_pathogenic	0.8745	pathogenic	-0.324	Destabilizing	1.0	D	0.593	neutral	D	0.677981723	None	None	N
D/F	0.9945	likely_pathogenic	0.994	pathogenic	1.02	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/G	0.9637	likely_pathogenic	0.9712	pathogenic	-0.154	Destabilizing	1.0	D	0.777	deleterious	D	0.712890954	None	None	N
D/H	0.9216	likely_pathogenic	0.94	pathogenic	0.77	Stabilizing	1.0	D	0.827	deleterious	D	0.654213949	None	None	N
D/I	0.9935	likely_pathogenic	0.9945	pathogenic	1.588	Stabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
D/K	0.9847	likely_pathogenic	0.9873	pathogenic	0.525	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/L	0.9874	likely_pathogenic	0.988	pathogenic	1.588	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
D/M	0.9959	likely_pathogenic	0.9959	pathogenic	1.958	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/N	0.8563	likely_pathogenic	0.8846	pathogenic	-0.316	Destabilizing	1.0	D	0.757	deleterious	D	0.678364618	None	None	N
D/P	0.9971	likely_pathogenic	0.9977	pathogenic	1.194	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
D/Q	0.9712	likely_pathogenic	0.9744	pathogenic	0.005	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
D/R	0.9863	likely_pathogenic	0.9885	pathogenic	0.509	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
D/S	0.932	likely_pathogenic	0.9457	pathogenic	-0.649	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/T	0.9857	likely_pathogenic	0.9875	pathogenic	-0.206	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
D/V	0.9794	likely_pathogenic	0.9821	pathogenic	1.194	Stabilizing	1.0	D	0.833	deleterious	D	0.712902225	None	None	N
D/W	0.998	likely_pathogenic	0.998	pathogenic	1.132	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
D/Y	0.9667	likely_pathogenic	0.9693	pathogenic	1.352	Stabilizing	1.0	D	0.841	deleterious	D	0.712976599	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.