TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16209	48850;48851;48852	chr2:178615320;178615319;178615318	chr2:179480047;179480046;179480045
N2AB	14568	43927;43928;43929	chr2:178615320;178615319;178615318	chr2:179480047;179480046;179480045
N2A	13641	41146;41147;41148	chr2:178615320;178615319;178615318	chr2:179480047;179480046;179480045
N2B	7144	21655;21656;21657	chr2:178615320;178615319;178615318	chr2:179480047;179480046;179480045
Novex-1	7269	22030;22031;22032	chr2:178615320;178615319;178615318	chr2:179480047;179480046;179480045
Novex-2	7336	22231;22232;22233	chr2:178615320;178615319;178615318	chr2:179480047;179480046;179480045
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: Fn3-5
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.186
• 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	None	None	0.656	N	0.504	0.123	0.47432691512	gnomAD-4.0.0	1.59457E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8826E-05	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	0.1798	likely_benign	0.1673	benign	-1.551	Destabilizing	0.656	D	0.504	neutral	N	0.475346037	None	None	N
V/C	0.6889	likely_pathogenic	0.6835	pathogenic	-0.911	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
V/D	0.6515	likely_pathogenic	0.6145	pathogenic	-1.408	Destabilizing	0.97	D	0.7	prob.neutral	D	0.551384499	None	None	N
V/E	0.4773	ambiguous	0.4324	ambiguous	-1.332	Destabilizing	0.978	D	0.621	neutral	None	None	None	None	N
V/F	0.2696	likely_benign	0.2501	benign	-1.013	Destabilizing	0.942	D	0.625	neutral	D	0.548073778	None	None	N
V/G	0.2841	likely_benign	0.2648	benign	-1.951	Destabilizing	0.97	D	0.639	neutral	N	0.466609496	None	None	N
V/H	0.6289	likely_pathogenic	0.6016	pathogenic	-1.554	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
V/I	0.0922	likely_benign	0.0893	benign	-0.517	Destabilizing	0.014	N	0.271	neutral	N	0.471760314	None	None	N
V/K	0.3714	ambiguous	0.3542	ambiguous	-1.247	Destabilizing	0.978	D	0.609	neutral	None	None	None	None	N
V/L	0.2048	likely_benign	0.1837	benign	-0.517	Destabilizing	0.247	N	0.355	neutral	N	0.476207523	None	None	N
V/M	0.1624	likely_benign	0.1467	benign	-0.38	Destabilizing	0.356	N	0.233	neutral	None	None	None	None	N
V/N	0.4224	ambiguous	0.4071	ambiguous	-1.151	Destabilizing	0.978	D	0.718	prob.delet.	None	None	None	None	N
V/P	0.8314	likely_pathogenic	0.792	pathogenic	-0.828	Destabilizing	0.993	D	0.664	neutral	None	None	None	None	N
V/Q	0.3505	ambiguous	0.3264	benign	-1.202	Destabilizing	0.978	D	0.674	neutral	None	None	None	None	N
V/R	0.3714	ambiguous	0.3438	ambiguous	-0.872	Destabilizing	0.978	D	0.719	prob.delet.	None	None	None	None	N
V/S	0.2606	likely_benign	0.249	benign	-1.732	Destabilizing	0.754	D	0.591	neutral	None	None	None	None	N
V/T	0.1628	likely_benign	0.1547	benign	-1.533	Destabilizing	0.076	N	0.266	neutral	None	None	None	None	N
V/W	0.9067	likely_pathogenic	0.884	pathogenic	-1.331	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
V/Y	0.7144	likely_pathogenic	0.6932	pathogenic	-0.981	Destabilizing	0.978	D	0.647	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.