TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15694	47305;47306;47307	chr2:178618378;178618377;178618376	chr2:179483105;179483104;179483103
N2AB	14053	42382;42383;42384	chr2:178618378;178618377;178618376	chr2:179483105;179483104;179483103
N2A	13126	39601;39602;39603	chr2:178618378;178618377;178618376	chr2:179483105;179483104;179483103
N2B	6629	20110;20111;20112	chr2:178618378;178618377;178618376	chr2:179483105;179483104;179483103
Novex-1	6754	20485;20486;20487	chr2:178618378;178618377;178618376	chr2:179483105;179483104;179483103
Novex-2	6821	20686;20687;20688	chr2:178618378;178618377;178618376	chr2:179483105;179483104;179483103
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: 38
• Structural Position: 40
• Q(SASA): 0.0895
• 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/I	None	None	0.046	N	0.269	0.097	0.406806705197	gnomAD-4.0.0	1.59393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	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	0.8474	likely_pathogenic	0.8877	pathogenic	-2.016	Highly Destabilizing	0.939	D	0.608	neutral	D	0.667477474	None	None	N
V/C	0.9745	likely_pathogenic	0.9764	pathogenic	-1.377	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
V/D	0.999	likely_pathogenic	0.9986	pathogenic	-2.881	Highly Destabilizing	0.997	D	0.905	deleterious	D	0.765805413	None	None	N
V/E	0.9951	likely_pathogenic	0.9941	pathogenic	-2.547	Highly Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
V/F	0.9054	likely_pathogenic	0.9191	pathogenic	-1.044	Destabilizing	0.982	D	0.767	deleterious	D	0.765729594	None	None	N
V/G	0.9634	likely_pathogenic	0.9579	pathogenic	-2.651	Highly Destabilizing	0.997	D	0.898	deleterious	D	0.765805413	None	None	N
V/H	0.9988	likely_pathogenic	0.9988	pathogenic	-2.661	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
V/I	0.0733	likely_benign	0.0905	benign	-0.169	Destabilizing	0.046	N	0.269	neutral	N	0.471771377	None	None	N
V/K	0.9965	likely_pathogenic	0.9955	pathogenic	-1.411	Destabilizing	0.993	D	0.878	deleterious	None	None	None	None	N
V/L	0.4678	ambiguous	0.58	pathogenic	-0.169	Destabilizing	0.046	N	0.327	neutral	N	0.500877172	None	None	N
V/M	0.6831	likely_pathogenic	0.7943	pathogenic	-0.485	Destabilizing	0.986	D	0.664	neutral	None	None	None	None	N
V/N	0.9958	likely_pathogenic	0.9956	pathogenic	-2.11	Highly Destabilizing	0.998	D	0.914	deleterious	None	None	None	None	N
V/P	0.9949	likely_pathogenic	0.9939	pathogenic	-0.765	Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
V/Q	0.9946	likely_pathogenic	0.9942	pathogenic	-1.703	Destabilizing	0.998	D	0.903	deleterious	None	None	None	None	N
V/R	0.9937	likely_pathogenic	0.9911	pathogenic	-1.702	Destabilizing	0.998	D	0.914	deleterious	None	None	None	None	N
V/S	0.9798	likely_pathogenic	0.9814	pathogenic	-2.631	Highly Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
V/T	0.8816	likely_pathogenic	0.8989	pathogenic	-2.125	Highly Destabilizing	0.953	D	0.634	neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9988	pathogenic	-1.62	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/Y	0.9947	likely_pathogenic	0.9951	pathogenic	-1.252	Destabilizing	0.998	D	0.77	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.