TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28959	87100;87101;87102	chr2:178558584;178558583;178558582	chr2:179423311;179423310;179423309
N2AB	27318	82177;82178;82179	chr2:178558584;178558583;178558582	chr2:179423311;179423310;179423309
N2A	26391	79396;79397;79398	chr2:178558584;178558583;178558582	chr2:179423311;179423310;179423309
N2B	19894	59905;59906;59907	chr2:178558584;178558583;178558582	chr2:179423311;179423310;179423309
Novex-1	20019	60280;60281;60282	chr2:178558584;178558583;178558582	chr2:179423311;179423310;179423309
Novex-2	20086	60481;60482;60483	chr2:178558584;178558583;178558582	chr2:179423311;179423310;179423309
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: Fn3-99
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0855
• 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/A	rs752544445	-2.222	0.922	N	0.605	0.299	0.507031862817	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
V/A	rs752544445	-2.222	0.922	N	0.605	0.299	0.507031862817	gnomAD-4.0.0	2.0528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69842E-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	0.2467	likely_benign	0.2547	benign	-1.899	Destabilizing	0.922	D	0.605	neutral	N	0.492951213	None	None	N
V/C	0.828	likely_pathogenic	0.8462	pathogenic	-1.928	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/D	0.995	likely_pathogenic	0.9946	pathogenic	-1.824	Destabilizing	1.0	D	0.869	deleterious	D	0.5286382	None	None	N
V/E	0.9881	likely_pathogenic	0.9874	pathogenic	-1.533	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/F	0.6797	likely_pathogenic	0.6952	pathogenic	-1.206	Destabilizing	0.987	D	0.845	deleterious	N	0.507999049	None	None	N
V/G	0.7377	likely_pathogenic	0.7441	pathogenic	-2.487	Highly Destabilizing	0.996	D	0.87	deleterious	N	0.520876292	None	None	N
V/H	0.9942	likely_pathogenic	0.9944	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/I	0.0902	likely_benign	0.0894	benign	-0.215	Destabilizing	0.015	N	0.209	neutral	N	0.509515389	None	None	N
V/K	0.9912	likely_pathogenic	0.9909	pathogenic	-1.352	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/L	0.3386	likely_benign	0.335	benign	-0.215	Destabilizing	0.116	N	0.482	neutral	N	0.515763784	None	None	N
V/M	0.3911	ambiguous	0.3937	ambiguous	-0.677	Destabilizing	0.987	D	0.742	deleterious	None	None	None	None	N
V/N	0.9778	likely_pathogenic	0.978	pathogenic	-1.852	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
V/P	0.992	likely_pathogenic	0.9911	pathogenic	-0.754	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
V/Q	0.9806	likely_pathogenic	0.9807	pathogenic	-1.489	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/R	0.981	likely_pathogenic	0.9803	pathogenic	-1.602	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/S	0.7862	likely_pathogenic	0.7977	pathogenic	-2.598	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/T	0.5901	likely_pathogenic	0.6229	pathogenic	-2.12	Highly Destabilizing	0.995	D	0.68	prob.neutral	None	None	None	None	N
V/W	0.9961	likely_pathogenic	0.9963	pathogenic	-1.538	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/Y	0.9723	likely_pathogenic	0.9735	pathogenic	-1.198	Destabilizing	1.0	D	0.842	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.