TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23805	71638;71639;71640	chr2:178574719;178574718;178574717	chr2:179439446;179439445;179439444
N2AB	22164	66715;66716;66717	chr2:178574719;178574718;178574717	chr2:179439446;179439445;179439444
N2A	21237	63934;63935;63936	chr2:178574719;178574718;178574717	chr2:179439446;179439445;179439444
N2B	14740	44443;44444;44445	chr2:178574719;178574718;178574717	chr2:179439446;179439445;179439444
Novex-1	14865	44818;44819;44820	chr2:178574719;178574718;178574717	chr2:179439446;179439445;179439444
Novex-2	14932	45019;45020;45021	chr2:178574719;178574718;178574717	chr2:179439446;179439445;179439444
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-60
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.0826
• 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
N/K	None	None	0.977	D	0.695	0.514	0.146414634003	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
N/A	0.9991	likely_pathogenic	0.9987	pathogenic	-1.524	Destabilizing	0.983	D	0.75	deleterious	None	None	None	None	N
N/C	0.9752	likely_pathogenic	0.9644	pathogenic	-1.016	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
N/D	0.9958	likely_pathogenic	0.9942	pathogenic	-2.246	Highly Destabilizing	0.977	D	0.595	neutral	D	0.541123822	None	None	N
N/E	0.9993	likely_pathogenic	0.9993	pathogenic	-2.017	Highly Destabilizing	0.983	D	0.629	neutral	None	None	None	None	N
N/F	0.9997	likely_pathogenic	0.9997	pathogenic	-1.185	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
N/G	0.9941	likely_pathogenic	0.9926	pathogenic	-1.851	Destabilizing	0.983	D	0.553	neutral	None	None	None	None	N
N/H	0.9923	likely_pathogenic	0.9891	pathogenic	-1.361	Destabilizing	0.235	N	0.403	neutral	D	0.542898248	None	None	N
N/I	0.9984	likely_pathogenic	0.998	pathogenic	-0.652	Destabilizing	0.997	D	0.779	deleterious	D	0.554508043	None	None	N
N/K	0.9994	likely_pathogenic	0.9993	pathogenic	-0.542	Destabilizing	0.977	D	0.695	prob.neutral	D	0.54188429	None	None	N
N/L	0.9938	likely_pathogenic	0.993	pathogenic	-0.652	Destabilizing	0.995	D	0.788	deleterious	None	None	None	None	N
N/M	0.9975	likely_pathogenic	0.9966	pathogenic	-0.575	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/P	0.9994	likely_pathogenic	0.9995	pathogenic	-0.921	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
N/Q	0.9992	likely_pathogenic	0.9989	pathogenic	-1.123	Destabilizing	0.995	D	0.758	deleterious	None	None	None	None	N
N/R	0.9988	likely_pathogenic	0.9989	pathogenic	-0.644	Destabilizing	0.995	D	0.763	deleterious	None	None	None	None	N
N/S	0.9528	likely_pathogenic	0.9205	pathogenic	-1.45	Destabilizing	0.977	D	0.562	neutral	N	0.509168046	None	None	N
N/T	0.9893	likely_pathogenic	0.984	pathogenic	-1.069	Destabilizing	0.989	D	0.698	prob.neutral	N	0.494124756	None	None	N
N/V	0.9974	likely_pathogenic	0.9965	pathogenic	-0.921	Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.17	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
N/Y	0.9968	likely_pathogenic	0.9963	pathogenic	-0.819	Destabilizing	0.993	D	0.773	deleterious	D	0.554254554	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.