TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15657	47194;47195;47196	chr2:178618489;178618488;178618487	chr2:179483216;179483215;179483214
N2AB	14016	42271;42272;42273	chr2:178618489;178618488;178618487	chr2:179483216;179483215;179483214
N2A	13089	39490;39491;39492	chr2:178618489;178618488;178618487	chr2:179483216;179483215;179483214
N2B	6592	19999;20000;20001	chr2:178618489;178618488;178618487	chr2:179483216;179483215;179483214
Novex-1	6717	20374;20375;20376	chr2:178618489;178618488;178618487	chr2:179483216;179483215;179483214
Novex-2	6784	20575;20576;20577	chr2:178618489;178618488;178618487	chr2:179483216;179483215;179483214
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: Fn3-1
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3799
• Predicted PPI site: I

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/I	rs1367129702	-0.326	0.994	N	0.51	0.168	0.557365556891	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	2.95E-05	None	0	0	None	0	None	0	0	0
V/I	rs1367129702	-0.326	0.994	N	0.51	0.168	0.557365556891	gnomAD-4.0.0	1.37085E-06	None	None	None	None	I	None	0	2.2605E-05	None	0	0	None	0	0	0	0	1.66118E-05

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	0.2837	likely_benign	0.3119	benign	-0.546	Destabilizing	0.997	D	0.441	neutral	N	0.477238329	None	None	I
V/C	0.7337	likely_pathogenic	0.7686	pathogenic	-0.731	Destabilizing	1.0	D	0.672	prob.neutral	None	None	None	None	I
V/D	0.6778	likely_pathogenic	0.6894	pathogenic	0.022	Stabilizing	0.999	D	0.805	deleterious	D	0.590167166	None	None	I
V/E	0.4273	ambiguous	0.4761	ambiguous	-0.081	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	I
V/F	0.3547	ambiguous	0.3587	ambiguous	-0.823	Destabilizing	0.999	D	0.671	prob.neutral	D	0.526608346	None	None	I
V/G	0.4502	ambiguous	0.4841	ambiguous	-0.667	Destabilizing	0.999	D	0.768	deleterious	D	0.589262482	None	None	I
V/H	0.7252	likely_pathogenic	0.7627	pathogenic	-0.241	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
V/I	0.083	likely_benign	0.0944	benign	-0.375	Destabilizing	0.994	D	0.51	neutral	N	0.434184949	None	None	I
V/K	0.3186	likely_benign	0.3479	ambiguous	-0.176	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	I
V/L	0.3378	likely_benign	0.3849	ambiguous	-0.375	Destabilizing	0.994	D	0.506	neutral	N	0.468143862	None	None	I
V/M	0.2264	likely_benign	0.2749	benign	-0.333	Destabilizing	0.999	D	0.659	prob.neutral	None	None	None	None	I
V/N	0.4457	ambiguous	0.4622	ambiguous	-0.005	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	I
V/P	0.736	likely_pathogenic	0.7572	pathogenic	-0.398	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
V/Q	0.4049	ambiguous	0.4494	ambiguous	-0.264	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
V/R	0.3319	likely_benign	0.3655	ambiguous	0.252	Stabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
V/S	0.3633	ambiguous	0.382	ambiguous	-0.456	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
V/T	0.1931	likely_benign	0.215	benign	-0.458	Destabilizing	0.998	D	0.668	prob.neutral	None	None	None	None	I
V/W	0.9434	likely_pathogenic	0.9554	pathogenic	-0.848	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
V/Y	0.7457	likely_pathogenic	0.7518	pathogenic	-0.512	Destabilizing	0.999	D	0.704	prob.delet.	None	None	None	None	I

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.