TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24284	73075;73076;73077	chr2:178573282;178573281;178573280	chr2:179438009;179438008;179438007
N2AB	22643	68152;68153;68154	chr2:178573282;178573281;178573280	chr2:179438009;179438008;179438007
N2A	21716	65371;65372;65373	chr2:178573282;178573281;178573280	chr2:179438009;179438008;179438007
N2B	15219	45880;45881;45882	chr2:178573282;178573281;178573280	chr2:179438009;179438008;179438007
Novex-1	15344	46255;46256;46257	chr2:178573282;178573281;178573280	chr2:179438009;179438008;179438007
Novex-2	15411	46456;46457;46458	chr2:178573282;178573281;178573280	chr2:179438009;179438008;179438007
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: Fn3-64
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.11
• 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	rs755011962	-0.163	0.973	N	0.665	0.266	0.575147286571	gnomAD-2.1.1	4.27E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.82E-05	0	0
V/L	rs755011962	-0.163	0.973	N	0.665	0.266	0.575147286571	gnomAD-4.0.0	1.6398E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.90121E-05	0	0	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	0.3479	ambiguous	0.3509	ambiguous	-1.827	Destabilizing	0.543	D	0.333	neutral	N	0.518583163	None	None	N
V/C	0.8594	likely_pathogenic	0.8449	pathogenic	-1.329	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/D	0.9771	likely_pathogenic	0.9794	pathogenic	-1.961	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
V/E	0.9574	likely_pathogenic	0.9592	pathogenic	-1.74	Destabilizing	0.998	D	0.849	deleterious	D	0.551505849	None	None	N
V/F	0.6605	likely_pathogenic	0.6708	pathogenic	-1.061	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/G	0.7087	likely_pathogenic	0.6993	pathogenic	-2.375	Highly Destabilizing	0.997	D	0.816	deleterious	D	0.539984959	None	None	N
V/H	0.984	likely_pathogenic	0.9835	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/I	0.1093	likely_benign	0.1135	benign	-0.308	Destabilizing	0.99	D	0.559	neutral	None	None	None	None	N
V/K	0.9816	likely_pathogenic	0.9821	pathogenic	-1.431	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
V/L	0.5538	ambiguous	0.564	ambiguous	-0.308	Destabilizing	0.973	D	0.665	neutral	N	0.512187548	None	None	N
V/M	0.5226	ambiguous	0.5337	ambiguous	-0.351	Destabilizing	0.999	D	0.726	prob.delet.	D	0.524500824	None	None	N
V/N	0.9183	likely_pathogenic	0.924	pathogenic	-1.699	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/P	0.9656	likely_pathogenic	0.9663	pathogenic	-0.785	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/Q	0.9554	likely_pathogenic	0.957	pathogenic	-1.514	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/R	0.9738	likely_pathogenic	0.9723	pathogenic	-1.363	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
V/S	0.6901	likely_pathogenic	0.6972	pathogenic	-2.389	Highly Destabilizing	0.995	D	0.815	deleterious	None	None	None	None	N
V/T	0.611	likely_pathogenic	0.6136	pathogenic	-2.006	Highly Destabilizing	0.992	D	0.667	neutral	None	None	None	None	N
V/W	0.993	likely_pathogenic	0.992	pathogenic	-1.519	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9503	likely_pathogenic	0.9487	pathogenic	-1.104	Destabilizing	1.0	D	0.796	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.