TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29546	88861;88862;88863	chr2:178554711;178554710;178554709	chr2:179419438;179419437;179419436
N2AB	27905	83938;83939;83940	chr2:178554711;178554710;178554709	chr2:179419438;179419437;179419436
N2A	26978	81157;81158;81159	chr2:178554711;178554710;178554709	chr2:179419438;179419437;179419436
N2B	20481	61666;61667;61668	chr2:178554711;178554710;178554709	chr2:179419438;179419437;179419436
Novex-1	20606	62041;62042;62043	chr2:178554711;178554710;178554709	chr2:179419438;179419437;179419436
Novex-2	20673	62242;62243;62244	chr2:178554711;178554710;178554709	chr2:179419438;179419437;179419436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-103
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.2708
• 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	rs758393823	-0.687	0.046	N	0.208	0.064	0.410204130746	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/I	rs758393823	-0.687	0.046	N	0.208	0.064	0.410204130746	gnomAD-4.0.0	7.52593E-06	None	None	None	None	N	None	0	0	None	0	5.03854E-05	None	0	0	6.29595E-06	1.15955E-05	1.65651E-05

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	0.5795	likely_pathogenic	0.5576	ambiguous	-1.602	Destabilizing	0.939	D	0.441	neutral	D	0.524082196	None	None	N
V/C	0.8923	likely_pathogenic	0.8883	pathogenic	-1.546	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
V/D	0.9504	likely_pathogenic	0.9422	pathogenic	-1.601	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
V/E	0.8392	likely_pathogenic	0.8181	pathogenic	-1.571	Destabilizing	0.997	D	0.757	deleterious	N	0.49952958	None	None	N
V/F	0.5793	likely_pathogenic	0.5828	pathogenic	-1.395	Destabilizing	0.986	D	0.744	deleterious	None	None	None	None	N
V/G	0.8038	likely_pathogenic	0.7832	pathogenic	-1.941	Destabilizing	0.997	D	0.803	deleterious	N	0.516192257	None	None	N
V/H	0.9397	likely_pathogenic	0.9368	pathogenic	-1.552	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
V/I	0.0716	likely_benign	0.0747	benign	-0.753	Destabilizing	0.046	N	0.208	neutral	N	0.459972003	None	None	N
V/K	0.7944	likely_pathogenic	0.7716	pathogenic	-1.227	Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N
V/L	0.4169	ambiguous	0.4097	ambiguous	-0.753	Destabilizing	0.76	D	0.332	neutral	N	0.468801572	None	None	N
V/M	0.2731	likely_benign	0.2707	benign	-0.753	Destabilizing	0.986	D	0.666	neutral	None	None	None	None	N
V/N	0.8334	likely_pathogenic	0.8233	pathogenic	-1.163	Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
V/P	0.9608	likely_pathogenic	0.9586	pathogenic	-1.003	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
V/Q	0.7674	likely_pathogenic	0.7513	pathogenic	-1.313	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
V/R	0.773	likely_pathogenic	0.7453	pathogenic	-0.824	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
V/S	0.7474	likely_pathogenic	0.7282	pathogenic	-1.761	Destabilizing	0.993	D	0.755	deleterious	None	None	None	None	N
V/T	0.5135	ambiguous	0.4885	ambiguous	-1.609	Destabilizing	0.953	D	0.547	neutral	None	None	None	None	N
V/W	0.9786	likely_pathogenic	0.9785	pathogenic	-1.597	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/Y	0.9126	likely_pathogenic	0.9077	pathogenic	-1.255	Destabilizing	0.998	D	0.76	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.