TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15876	47851;47852;47853	chr2:178617459;178617458;178617457	chr2:179482186;179482185;179482184
N2AB	14235	42928;42929;42930	chr2:178617459;178617458;178617457	chr2:179482186;179482185;179482184
N2A	13308	40147;40148;40149	chr2:178617459;178617458;178617457	chr2:179482186;179482185;179482184
N2B	6811	20656;20657;20658	chr2:178617459;178617458;178617457	chr2:179482186;179482185;179482184
Novex-1	6936	21031;21032;21033	chr2:178617459;178617458;178617457	chr2:179482186;179482185;179482184
Novex-2	7003	21232;21233;21234	chr2:178617459;178617458;178617457	chr2:179482186;179482185;179482184
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-3
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0798
• 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/F	None	None	0.999	D	0.824	0.395	0.64127314462	gnomAD-4.0.0	6.91052E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02897E-07	0	0
V/I	rs766025438	-0.98	0.973	N	0.536	0.236	0.389750110748	gnomAD-2.1.1	4.33E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.37E-06	0
V/I	rs766025438	-0.98	0.973	N	0.536	0.236	0.389750110748	gnomAD-4.0.0	1.65852E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.16695E-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
V/A	0.3613	ambiguous	0.4332	ambiguous	-2.472	Highly Destabilizing	0.948	D	0.62	neutral	N	0.481192689	None	None	N
V/C	0.734	likely_pathogenic	0.766	pathogenic	-2.713	Highly Destabilizing	0.296	N	0.472	neutral	None	None	None	None	N
V/D	0.9191	likely_pathogenic	0.95	pathogenic	-3.344	Highly Destabilizing	0.999	D	0.856	deleterious	D	0.716024008	None	None	N
V/E	0.8378	likely_pathogenic	0.8879	pathogenic	-3.111	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/F	0.3364	likely_benign	0.3991	ambiguous	-1.6	Destabilizing	0.999	D	0.824	deleterious	D	0.595895062	None	None	N
V/G	0.5431	ambiguous	0.6187	pathogenic	-3.004	Highly Destabilizing	0.997	D	0.847	deleterious	D	0.676847475	None	None	N
V/H	0.9064	likely_pathogenic	0.9393	pathogenic	-2.619	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/I	0.0771	likely_benign	0.0844	benign	-0.969	Destabilizing	0.973	D	0.536	neutral	N	0.457856344	None	None	N
V/K	0.8766	likely_pathogenic	0.9164	pathogenic	-2.111	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/L	0.2638	likely_benign	0.3134	benign	-0.969	Destabilizing	0.948	D	0.623	neutral	N	0.470919028	None	None	N
V/M	0.2643	likely_benign	0.3109	benign	-1.425	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
V/N	0.7582	likely_pathogenic	0.8362	pathogenic	-2.602	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/P	0.98	likely_pathogenic	0.9854	pathogenic	-1.447	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
V/Q	0.7885	likely_pathogenic	0.8395	pathogenic	-2.443	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
V/R	0.7949	likely_pathogenic	0.8454	pathogenic	-1.899	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
V/S	0.5562	ambiguous	0.6471	pathogenic	-3.228	Highly Destabilizing	0.998	D	0.826	deleterious	None	None	None	None	N
V/T	0.4062	ambiguous	0.4924	ambiguous	-2.843	Highly Destabilizing	0.992	D	0.684	prob.neutral	None	None	None	None	N
V/W	0.9544	likely_pathogenic	0.9693	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.8223	likely_pathogenic	0.8701	pathogenic	-1.725	Destabilizing	0.999	D	0.83	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.