TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17108	51547;51548;51549	chr2:178610204;178610203;178610202	chr2:179474931;179474930;179474929
N2AB	15467	46624;46625;46626	chr2:178610204;178610203;178610202	chr2:179474931;179474930;179474929
N2A	14540	43843;43844;43845	chr2:178610204;178610203;178610202	chr2:179474931;179474930;179474929
N2B	8043	24352;24353;24354	chr2:178610204;178610203;178610202	chr2:179474931;179474930;179474929
Novex-1	8168	24727;24728;24729	chr2:178610204;178610203;178610202	chr2:179474931;179474930;179474929
Novex-2	8235	24928;24929;24930	chr2:178610204;178610203;178610202	chr2:179474931;179474930;179474929
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: Fn3-12
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1277
• 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/M	None	None	1.0	N	0.751	0.44	0.66694160307	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93752E-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
V/A	0.8206	likely_pathogenic	0.7848	pathogenic	-1.937	Destabilizing	0.999	D	0.651	neutral	D	0.527472005	None	None	N
V/C	0.9491	likely_pathogenic	0.9426	pathogenic	-1.461	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9974	pathogenic	-2.239	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/E	0.9864	likely_pathogenic	0.987	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.822	deleterious	D	0.543112058	None	None	N
V/F	0.845	likely_pathogenic	0.8711	pathogenic	-1.15	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/G	0.9616	likely_pathogenic	0.9484	pathogenic	-2.484	Highly Destabilizing	1.0	D	0.834	deleterious	N	0.520399447	None	None	N
V/H	0.9961	likely_pathogenic	0.996	pathogenic	-2.205	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/I	0.0994	likely_benign	0.1119	benign	-0.419	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
V/K	0.9935	likely_pathogenic	0.9927	pathogenic	-1.63	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/L	0.609	likely_pathogenic	0.6764	pathogenic	-0.419	Destabilizing	0.997	D	0.662	neutral	N	0.517844084	None	None	N
V/M	0.6277	likely_pathogenic	0.691	pathogenic	-0.434	Destabilizing	1.0	D	0.751	deleterious	N	0.513144518	None	None	N
V/N	0.989	likely_pathogenic	0.9894	pathogenic	-1.891	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/P	0.9887	likely_pathogenic	0.982	pathogenic	-0.896	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Q	0.985	likely_pathogenic	0.9837	pathogenic	-1.726	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/R	0.9899	likely_pathogenic	0.9885	pathogenic	-1.498	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/S	0.961	likely_pathogenic	0.9545	pathogenic	-2.556	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/T	0.8816	likely_pathogenic	0.8746	pathogenic	-2.181	Highly Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
V/W	0.9976	likely_pathogenic	0.998	pathogenic	-1.626	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/Y	0.989	likely_pathogenic	0.9903	pathogenic	-1.222	Destabilizing	1.0	D	0.789	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.