TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8258	24997;24998;24999	chr2:178718334;178718333;178718332	chr2:179583061;179583060;179583059
N2AB	7941	24046;24047;24048	chr2:178718334;178718333;178718332	chr2:179583061;179583060;179583059
N2A	7014	21265;21266;21267	chr2:178718334;178718333;178718332	chr2:179583061;179583060;179583059
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-67
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.141
• 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
V/L	None	None	0.117	N	0.291	0.109	0.263140351381	gnomAD-4.0.0	6.84451E-07	None	None	None	None	N	None	0	0	None	0	2.52003E-05	None	0	0	0	0	0
V/M	None	None	0.993	N	0.751	0.347	0.496693547531	gnomAD-4.0.0	1.3689E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99735E-07	1.16015E-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
V/A	0.8417	likely_pathogenic	0.832	pathogenic	-2.106	Highly Destabilizing	0.977	D	0.635	neutral	N	0.501720582	None	None	N
V/C	0.9687	likely_pathogenic	0.9635	pathogenic	-1.381	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/D	0.9955	likely_pathogenic	0.9958	pathogenic	-2.911	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
V/E	0.9857	likely_pathogenic	0.9853	pathogenic	-2.59	Highly Destabilizing	0.999	D	0.857	deleterious	N	0.513583867	None	None	N
V/F	0.7448	likely_pathogenic	0.7035	pathogenic	-1.207	Destabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
V/G	0.9172	likely_pathogenic	0.9229	pathogenic	-2.717	Highly Destabilizing	0.999	D	0.866	deleterious	N	0.513583867	None	None	N
V/H	0.9942	likely_pathogenic	0.993	pathogenic	-2.75	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.1	likely_benign	0.0882	benign	-0.333	Destabilizing	0.921	D	0.551	neutral	None	None	None	None	N
V/K	0.9886	likely_pathogenic	0.9884	pathogenic	-1.504	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
V/L	0.3812	ambiguous	0.3102	benign	-0.333	Destabilizing	0.117	N	0.291	neutral	N	0.448169702	None	None	N
V/M	0.6912	likely_pathogenic	0.6183	pathogenic	-0.56	Destabilizing	0.993	D	0.751	deleterious	N	0.512569909	None	None	N
V/N	0.9841	likely_pathogenic	0.9847	pathogenic	-2.17	Highly Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
V/P	0.9849	likely_pathogenic	0.9854	pathogenic	-0.905	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9837	likely_pathogenic	0.9824	pathogenic	-1.783	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/R	0.9798	likely_pathogenic	0.9806	pathogenic	-1.736	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
V/S	0.9607	likely_pathogenic	0.9624	pathogenic	-2.675	Highly Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
V/T	0.9032	likely_pathogenic	0.9066	pathogenic	-2.191	Highly Destabilizing	0.991	D	0.67	neutral	None	None	None	None	N
V/W	0.9957	likely_pathogenic	0.9935	pathogenic	-1.796	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9774	likely_pathogenic	0.9729	pathogenic	-1.43	Destabilizing	0.999	D	0.815	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.