TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32408	97447;97448;97449	chr2:178542534;178542533;178542532	chr2:179407261;179407260;179407259
N2AB	30767	92524;92525;92526	chr2:178542534;178542533;178542532	chr2:179407261;179407260;179407259
N2A	29840	89743;89744;89745	chr2:178542534;178542533;178542532	chr2:179407261;179407260;179407259
N2B	23343	70252;70253;70254	chr2:178542534;178542533;178542532	chr2:179407261;179407260;179407259
Novex-1	23468	70627;70628;70629	chr2:178542534;178542533;178542532	chr2:179407261;179407260;179407259
Novex-2	23535	70828;70829;70830	chr2:178542534;178542533;178542532	chr2:179407261;179407260;179407259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-124
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.5998
• 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
K/T	rs1251245923	-0.315	0.211	N	0.319	0.117	0.130388298395	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
K/T	rs1251245923	-0.315	0.211	N	0.319	0.117	0.130388298395	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs1251245923	-0.315	0.211	N	0.319	0.117	0.130388298395	gnomAD-4.0.0	6.5722E-06	None	None	None	None	N	None	2.41313E-05	0	None	0	0	None	0	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
K/A	0.233	likely_benign	0.222	benign	-0.365	Destabilizing	0.851	D	0.633	neutral	None	None	None	None	N
K/C	0.3513	ambiguous	0.3074	benign	-0.395	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/D	0.4644	ambiguous	0.4424	ambiguous	0.008	Stabilizing	0.976	D	0.659	neutral	None	None	None	None	N
K/E	0.1527	likely_benign	0.145	benign	0.099	Stabilizing	0.896	D	0.583	neutral	N	0.468650201	None	None	N
K/F	0.5445	ambiguous	0.5016	ambiguous	-0.117	Destabilizing	0.988	D	0.706	prob.neutral	None	None	None	None	N
K/G	0.3431	ambiguous	0.2906	benign	-0.708	Destabilizing	0.919	D	0.615	neutral	None	None	None	None	N
K/H	0.15	likely_benign	0.1381	benign	-1.092	Destabilizing	0.997	D	0.649	neutral	None	None	None	None	N
K/I	0.1694	likely_benign	0.1733	benign	0.508	Stabilizing	0.976	D	0.704	prob.neutral	None	None	None	None	N
K/L	0.2051	likely_benign	0.1964	benign	0.508	Stabilizing	0.851	D	0.609	neutral	None	None	None	None	N
K/M	0.1512	likely_benign	0.1539	benign	0.32	Stabilizing	0.999	D	0.638	neutral	N	0.495490655	None	None	N
K/N	0.2761	likely_benign	0.2716	benign	-0.3	Destabilizing	0.968	D	0.593	neutral	N	0.484512743	None	None	N
K/P	0.8852	likely_pathogenic	0.8617	pathogenic	0.248	Stabilizing	0.988	D	0.685	prob.neutral	None	None	None	None	N
K/Q	0.0871	likely_benign	0.0819	benign	-0.36	Destabilizing	0.968	D	0.603	neutral	N	0.511862261	None	None	N
K/R	0.0654	likely_benign	0.0616	benign	-0.574	Destabilizing	0.026	N	0.21	neutral	N	0.471015716	None	None	N
K/S	0.2847	likely_benign	0.2634	benign	-0.89	Destabilizing	0.851	D	0.556	neutral	None	None	None	None	N
K/T	0.1121	likely_benign	0.1161	benign	-0.601	Destabilizing	0.211	N	0.319	neutral	N	0.473111871	None	None	N
K/V	0.1655	likely_benign	0.1666	benign	0.248	Stabilizing	0.952	D	0.629	neutral	None	None	None	None	N
K/W	0.5135	ambiguous	0.4186	ambiguous	-0.039	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
K/Y	0.4186	ambiguous	0.3683	ambiguous	0.253	Stabilizing	0.996	D	0.701	prob.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.