TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2867	8824;8825;8826	chr2:178770102;178770101;178770100	chr2:179634829;179634828;179634827
N2AB	2867	8824;8825;8826	chr2:178770102;178770101;178770100	chr2:179634829;179634828;179634827
N2A	2867	8824;8825;8826	chr2:178770102;178770101;178770100	chr2:179634829;179634828;179634827
N2B	2821	8686;8687;8688	chr2:178770102;178770101;178770100	chr2:179634829;179634828;179634827
Novex-1	2821	8686;8687;8688	chr2:178770102;178770101;178770100	chr2:179634829;179634828;179634827
Novex-2	2821	8686;8687;8688	chr2:178770102;178770101;178770100	chr2:179634829;179634828;179634827
Novex-3	2867	8824;8825;8826	chr2:178770102;178770101;178770100	chr2:179634829;179634828;179634827

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-18
• Domain position: 73
• Structural Position: 157
• Q(SASA): 0.133
• 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/M	None	None	0.02	D	0.434	0.19	0.441118900842	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	0.1594	likely_benign	0.2102	benign	-1.787	Destabilizing	0.055	N	0.585	neutral	D	0.542040284	None	None	N
V/C	0.6383	likely_pathogenic	0.7392	pathogenic	-1.274	Destabilizing	0.968	D	0.649	neutral	None	None	None	None	N
V/D	0.5164	ambiguous	0.6313	pathogenic	-1.889	Destabilizing	0.726	D	0.777	deleterious	None	None	None	None	N
V/E	0.2467	likely_benign	0.3218	benign	-1.767	Destabilizing	0.667	D	0.754	deleterious	N	0.50931781	None	None	N
V/F	0.1484	likely_benign	0.1911	benign	-1.136	Destabilizing	0.003	N	0.425	neutral	None	None	None	None	N
V/G	0.3145	likely_benign	0.4488	ambiguous	-2.241	Highly Destabilizing	0.497	N	0.751	deleterious	D	0.665640837	None	None	N
V/H	0.4182	ambiguous	0.5235	ambiguous	-1.919	Destabilizing	0.968	D	0.759	deleterious	None	None	None	None	N
V/I	0.0744	likely_benign	0.0754	benign	-0.578	Destabilizing	0.072	N	0.551	neutral	None	None	None	None	N
V/K	0.1853	likely_benign	0.2763	benign	-1.433	Destabilizing	0.567	D	0.745	deleterious	None	None	None	None	N
V/L	0.1149	likely_benign	0.1475	benign	-0.578	Destabilizing	0.001	N	0.354	neutral	N	0.507439841	None	None	N
V/M	0.0707	likely_benign	0.0831	benign	-0.525	Destabilizing	0.02	N	0.434	neutral	D	0.62750759	None	None	N
V/N	0.303	likely_benign	0.3868	ambiguous	-1.459	Destabilizing	0.726	D	0.78	deleterious	None	None	None	None	N
V/P	0.9691	likely_pathogenic	0.9833	pathogenic	-0.949	Destabilizing	0.89	D	0.752	deleterious	None	None	None	None	N
V/Q	0.1844	likely_benign	0.2545	benign	-1.448	Destabilizing	0.567	D	0.754	deleterious	None	None	None	None	N
V/R	0.1723	likely_benign	0.2664	benign	-1.135	Destabilizing	0.567	D	0.778	deleterious	None	None	None	None	N
V/S	0.2068	likely_benign	0.278	benign	-2.086	Highly Destabilizing	0.567	D	0.722	prob.delet.	None	None	None	None	N
V/T	0.1392	likely_benign	0.175	benign	-1.835	Destabilizing	0.272	N	0.564	neutral	None	None	None	None	N
V/W	0.6665	likely_pathogenic	0.7834	pathogenic	-1.531	Destabilizing	0.968	D	0.764	deleterious	None	None	None	None	N
V/Y	0.4864	ambiguous	0.5863	pathogenic	-1.17	Destabilizing	0.396	N	0.675	prob.neutral	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.