TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23439	70540;70541;70542	chr2:178575817;178575816;178575815	chr2:179440544;179440543;179440542
N2AB	21798	65617;65618;65619	chr2:178575817;178575816;178575815	chr2:179440544;179440543;179440542
N2A	20871	62836;62837;62838	chr2:178575817;178575816;178575815	chr2:179440544;179440543;179440542
N2B	14374	43345;43346;43347	chr2:178575817;178575816;178575815	chr2:179440544;179440543;179440542
Novex-1	14499	43720;43721;43722	chr2:178575817;178575816;178575815	chr2:179440544;179440543;179440542
Novex-2	14566	43921;43922;43923	chr2:178575817;178575816;178575815	chr2:179440544;179440543;179440542
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: Fn3-58
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0858
• 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	0.963	N	0.683	0.272	0.475506082792	gnomAD-4.0.0	6.8441E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99734E-07	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	0.426	ambiguous	0.4935	ambiguous	-2.133	Highly Destabilizing	0.963	D	0.683	prob.neutral	N	0.481979284	None	None	N
V/C	0.7891	likely_pathogenic	0.8094	pathogenic	-1.765	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/D	0.9933	likely_pathogenic	0.9954	pathogenic	-2.925	Highly Destabilizing	0.996	D	0.902	deleterious	N	0.48608877	None	None	N
V/E	0.9875	likely_pathogenic	0.9904	pathogenic	-2.709	Highly Destabilizing	0.997	D	0.872	deleterious	None	None	None	None	N
V/F	0.9464	likely_pathogenic	0.9576	pathogenic	-1.184	Destabilizing	0.996	D	0.839	deleterious	N	0.48634226	None	None	N
V/G	0.8393	likely_pathogenic	0.8707	pathogenic	-2.673	Highly Destabilizing	0.985	D	0.883	deleterious	N	0.48608877	None	None	N
V/H	0.9961	likely_pathogenic	0.9971	pathogenic	-2.45	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
V/I	0.1644	likely_benign	0.1723	benign	-0.621	Destabilizing	0.92	D	0.467	neutral	N	0.517630653	None	None	N
V/K	0.9951	likely_pathogenic	0.9963	pathogenic	-1.801	Destabilizing	0.997	D	0.876	deleterious	None	None	None	None	N
V/L	0.6703	likely_pathogenic	0.7047	pathogenic	-0.621	Destabilizing	0.92	D	0.549	neutral	N	0.474478975	None	None	N
V/M	0.7651	likely_pathogenic	0.8031	pathogenic	-0.764	Destabilizing	0.997	D	0.795	deleterious	None	None	None	None	N
V/N	0.9719	likely_pathogenic	0.9783	pathogenic	-2.121	Highly Destabilizing	0.997	D	0.903	deleterious	None	None	None	None	N
V/P	0.2249	likely_benign	0.2458	benign	-1.098	Destabilizing	0.997	D	0.878	deleterious	None	None	None	None	N
V/Q	0.9875	likely_pathogenic	0.9894	pathogenic	-1.968	Destabilizing	0.997	D	0.876	deleterious	None	None	None	None	N
V/R	0.9899	likely_pathogenic	0.9916	pathogenic	-1.631	Destabilizing	0.997	D	0.901	deleterious	None	None	None	None	N
V/S	0.8126	likely_pathogenic	0.852	pathogenic	-2.71	Highly Destabilizing	0.988	D	0.868	deleterious	None	None	None	None	N
V/T	0.6757	likely_pathogenic	0.719	pathogenic	-2.355	Highly Destabilizing	0.988	D	0.759	deleterious	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9995	pathogenic	-1.745	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
V/Y	0.9951	likely_pathogenic	0.9962	pathogenic	-1.38	Destabilizing	0.997	D	0.831	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.