TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32945	99058;99059;99060	chr2:178539102;178539101;178539100	chr2:179403829;179403828;179403827
N2AB	31304	94135;94136;94137	chr2:178539102;178539101;178539100	chr2:179403829;179403828;179403827
N2A	30377	91354;91355;91356	chr2:178539102;178539101;178539100	chr2:179403829;179403828;179403827
N2B	23880	71863;71864;71865	chr2:178539102;178539101;178539100	chr2:179403829;179403828;179403827
Novex-1	24005	72238;72239;72240	chr2:178539102;178539101;178539100	chr2:179403829;179403828;179403827
Novex-2	24072	72439;72440;72441	chr2:178539102;178539101;178539100	chr2:179403829;179403828;179403827
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-128
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.4458
• 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	None	None	0.997	N	0.545	0.32	0.418221603839	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6317	likely_pathogenic	0.6065	pathogenic	-1.151	Destabilizing	0.999	D	0.56	neutral	N	0.488716042	None	None	N
V/C	0.896	likely_pathogenic	0.8853	pathogenic	-0.773	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
V/D	0.8786	likely_pathogenic	0.8637	pathogenic	-0.932	Destabilizing	1.0	D	0.755	deleterious	N	0.50018383	None	None	N
V/E	0.6862	likely_pathogenic	0.6712	pathogenic	-0.963	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
V/F	0.3496	ambiguous	0.3362	benign	-0.888	Destabilizing	1.0	D	0.703	prob.neutral	N	0.45743313	None	None	N
V/G	0.6256	likely_pathogenic	0.6136	pathogenic	-1.414	Destabilizing	1.0	D	0.743	deleterious	N	0.472725138	None	None	N
V/H	0.846	likely_pathogenic	0.8356	pathogenic	-0.874	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/I	0.1002	likely_benign	0.0999	benign	-0.551	Destabilizing	0.997	D	0.491	neutral	N	0.467244692	None	None	N
V/K	0.7754	likely_pathogenic	0.7556	pathogenic	-1.058	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/L	0.4237	ambiguous	0.4225	ambiguous	-0.551	Destabilizing	0.997	D	0.545	neutral	N	0.472727869	None	None	N
V/M	0.3291	likely_benign	0.3223	benign	-0.477	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
V/N	0.6411	likely_pathogenic	0.6257	pathogenic	-0.822	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
V/P	0.9877	likely_pathogenic	0.9902	pathogenic	-0.716	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/Q	0.603	likely_pathogenic	0.5922	pathogenic	-1.015	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
V/R	0.7434	likely_pathogenic	0.7244	pathogenic	-0.484	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
V/S	0.6186	likely_pathogenic	0.5959	pathogenic	-1.274	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/T	0.5378	ambiguous	0.5061	ambiguous	-1.204	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
V/W	0.947	likely_pathogenic	0.9447	pathogenic	-1.039	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
V/Y	0.7831	likely_pathogenic	0.7726	pathogenic	-0.765	Destabilizing	1.0	D	0.712	prob.delet.	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.