TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14542	43849;43850;43851	chr2:178632270;178632269;178632268	chr2:179496997;179496996;179496995
N2AB	12901	38926;38927;38928	chr2:178632270;178632269;178632268	chr2:179496997;179496996;179496995
N2A	11974	36145;36146;36147	chr2:178632270;178632269;178632268	chr2:179496997;179496996;179496995
N2B	5477	16654;16655;16656	chr2:178632270;178632269;178632268	chr2:179496997;179496996;179496995
Novex-1	5602	17029;17030;17031	chr2:178632270;178632269;178632268	chr2:179496997;179496996;179496995
Novex-2	5669	17230;17231;17232	chr2:178632270;178632269;178632268	chr2:179496997;179496996;179496995
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: Ig-96
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1087
• 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	0.09	D	0.493	0.165	0.407767136052	gnomAD-4.0.0	1.60164E-06	None	None	None	None	N	None	0	0	None	4.804E-05	0	None	0	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	0.3952	ambiguous	0.3218	benign	-1.92	Destabilizing	0.581	D	0.515	neutral	D	0.634377103	None	None	N
V/C	0.8403	likely_pathogenic	0.7931	pathogenic	-1.776	Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
V/D	0.7733	likely_pathogenic	0.7064	pathogenic	-1.853	Destabilizing	0.908	D	0.827	deleterious	D	0.638155472	None	None	N
V/E	0.7134	likely_pathogenic	0.6436	pathogenic	-1.755	Destabilizing	0.929	D	0.792	deleterious	None	None	None	None	N
V/F	0.2	likely_benign	0.1631	benign	-1.464	Destabilizing	0.83	D	0.802	deleterious	N	0.50785307	None	None	N
V/G	0.5308	ambiguous	0.4621	ambiguous	-2.349	Highly Destabilizing	0.908	D	0.799	deleterious	D	0.635911604	None	None	N
V/H	0.8161	likely_pathogenic	0.7552	pathogenic	-1.94	Destabilizing	0.993	D	0.814	deleterious	None	None	None	None	N
V/I	0.0757	likely_benign	0.0706	benign	-0.787	Destabilizing	0.004	N	0.327	neutral	N	0.507974249	None	None	N
V/K	0.72	likely_pathogenic	0.6517	pathogenic	-1.482	Destabilizing	0.929	D	0.795	deleterious	None	None	None	None	N
V/L	0.2884	likely_benign	0.2296	benign	-0.787	Destabilizing	0.09	N	0.493	neutral	D	0.564443643	None	None	N
V/M	0.2299	likely_benign	0.2012	benign	-0.831	Destabilizing	0.866	D	0.757	deleterious	None	None	None	None	N
V/N	0.6275	likely_pathogenic	0.5409	ambiguous	-1.51	Destabilizing	0.976	D	0.833	deleterious	None	None	None	None	N
V/P	0.9136	likely_pathogenic	0.8879	pathogenic	-1.132	Destabilizing	0.976	D	0.812	deleterious	None	None	None	None	N
V/Q	0.7012	likely_pathogenic	0.6393	pathogenic	-1.552	Destabilizing	0.976	D	0.814	deleterious	None	None	None	None	N
V/R	0.6271	likely_pathogenic	0.5544	ambiguous	-1.135	Destabilizing	0.929	D	0.832	deleterious	None	None	None	None	N
V/S	0.5223	ambiguous	0.447	ambiguous	-2.195	Highly Destabilizing	0.929	D	0.782	deleterious	None	None	None	None	N
V/T	0.4017	ambiguous	0.3388	benign	-1.958	Destabilizing	0.648	D	0.601	neutral	None	None	None	None	N
V/W	0.9021	likely_pathogenic	0.8521	pathogenic	-1.729	Destabilizing	0.993	D	0.79	deleterious	None	None	None	None	N
V/Y	0.6631	likely_pathogenic	0.5686	pathogenic	-1.395	Destabilizing	0.929	D	0.81	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.