TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6014	18265;18266;18267	chr2:178730360;178730359;178730358	chr2:179595087;179595086;179595085
N2AB	5697	17314;17315;17316	chr2:178730360;178730359;178730358	chr2:179595087;179595086;179595085
N2A	4770	14533;14534;14535	chr2:178730360;178730359;178730358	chr2:179595087;179595086;179595085
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-44
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1716
• 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
F/S	None	None	0.998	D	0.847	0.773	0.847448009913	gnomAD-4.0.0	1.62806E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91812E-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
F/A	0.9563	likely_pathogenic	0.9552	pathogenic	-2.729	Highly Destabilizing	0.97	D	0.767	deleterious	None	None	None	None	N
F/C	0.9147	likely_pathogenic	0.9194	pathogenic	-1.426	Destabilizing	1.0	D	0.873	deleterious	D	0.5486411	None	None	N
F/D	0.9924	likely_pathogenic	0.9929	pathogenic	-2.495	Highly Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
F/E	0.9931	likely_pathogenic	0.9932	pathogenic	-2.347	Highly Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
F/G	0.9885	likely_pathogenic	0.9881	pathogenic	-3.112	Highly Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
F/H	0.9707	likely_pathogenic	0.9712	pathogenic	-1.426	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
F/I	0.4244	ambiguous	0.432	ambiguous	-1.509	Destabilizing	0.122	N	0.303	neutral	N	0.469722929	None	None	N
F/K	0.9954	likely_pathogenic	0.9955	pathogenic	-1.545	Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
F/L	0.9329	likely_pathogenic	0.9378	pathogenic	-1.509	Destabilizing	0.689	D	0.539	neutral	N	0.494640595	None	None	N
F/M	0.8098	likely_pathogenic	0.8222	pathogenic	-1.194	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
F/N	0.9843	likely_pathogenic	0.9856	pathogenic	-1.767	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
F/P	0.9942	likely_pathogenic	0.9941	pathogenic	-1.921	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
F/Q	0.9902	likely_pathogenic	0.9905	pathogenic	-1.849	Destabilizing	0.999	D	0.896	deleterious	None	None	None	None	N
F/R	0.9877	likely_pathogenic	0.9878	pathogenic	-0.923	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
F/S	0.9568	likely_pathogenic	0.9565	pathogenic	-2.474	Highly Destabilizing	0.998	D	0.847	deleterious	D	0.548134121	None	None	N
F/T	0.9446	likely_pathogenic	0.9448	pathogenic	-2.233	Highly Destabilizing	0.985	D	0.847	deleterious	None	None	None	None	N
F/V	0.5336	ambiguous	0.5372	ambiguous	-1.921	Destabilizing	0.835	D	0.626	neutral	N	0.504578095	None	None	N
F/W	0.8351	likely_pathogenic	0.8374	pathogenic	-0.37	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
F/Y	0.5647	likely_pathogenic	0.5722	pathogenic	-0.689	Destabilizing	0.993	D	0.685	prob.neutral	D	0.536866721	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.