TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33431	100516;100517;100518	chr2:178536456;178536455;178536454	chr2:179401183;179401182;179401181
N2AB	31790	95593;95594;95595	chr2:178536456;178536455;178536454	chr2:179401183;179401182;179401181
N2A	30863	92812;92813;92814	chr2:178536456;178536455;178536454	chr2:179401183;179401182;179401181
N2B	24366	73321;73322;73323	chr2:178536456;178536455;178536454	chr2:179401183;179401182;179401181
Novex-1	24491	73696;73697;73698	chr2:178536456;178536455;178536454	chr2:179401183;179401182;179401181
Novex-2	24558	73897;73898;73899	chr2:178536456;178536455;178536454	chr2:179401183;179401182;179401181
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: Fn3-131
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.088
• 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/M	rs369597353	-1.029	0.991	N	0.81	0.365	0.389283895039	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.37E-05	None	0	0	0
K/M	rs369597353	-1.029	0.991	N	0.81	0.365	0.389283895039	gnomAD-4.0.0	1.60731E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45049E-05	0
K/R	rs369597353	-0.629	0.01	N	0.4	0.109	None	gnomAD-2.1.1	8.18E-06	None	None	None	None	N	None	1.29769E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs369597353	-0.629	0.01	N	0.4	0.109	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.23E-05	0	0	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	0.9	likely_pathogenic	0.9199	pathogenic	-1.373	Destabilizing	0.648	D	0.694	prob.neutral	None	None	None	None	N
K/C	0.8603	likely_pathogenic	0.859	pathogenic	-1.415	Destabilizing	0.993	D	0.853	deleterious	None	None	None	None	N
K/D	0.9929	likely_pathogenic	0.9941	pathogenic	-2.25	Highly Destabilizing	0.866	D	0.795	deleterious	None	None	None	None	N
K/E	0.8188	likely_pathogenic	0.8654	pathogenic	-1.918	Destabilizing	0.41	N	0.657	neutral	N	0.500677987	None	None	N
K/F	0.9597	likely_pathogenic	0.9609	pathogenic	-0.687	Destabilizing	0.98	D	0.868	deleterious	None	None	None	None	N
K/G	0.9412	likely_pathogenic	0.9492	pathogenic	-1.856	Destabilizing	0.866	D	0.759	deleterious	None	None	None	None	N
K/H	0.785	likely_pathogenic	0.7756	pathogenic	-1.468	Destabilizing	0.98	D	0.82	deleterious	None	None	None	None	N
K/I	0.741	likely_pathogenic	0.7829	pathogenic	0.017	Stabilizing	0.929	D	0.88	deleterious	None	None	None	None	N
K/L	0.7551	likely_pathogenic	0.7745	pathogenic	0.017	Stabilizing	0.866	D	0.759	deleterious	None	None	None	None	N
K/M	0.5156	ambiguous	0.5512	ambiguous	-0.396	Destabilizing	0.991	D	0.81	deleterious	N	0.508629954	None	None	N
K/N	0.9539	likely_pathogenic	0.962	pathogenic	-2.001	Highly Destabilizing	0.83	D	0.789	deleterious	N	0.512198877	None	None	N
K/P	0.9984	likely_pathogenic	0.9985	pathogenic	-0.429	Destabilizing	0.929	D	0.822	deleterious	None	None	None	None	N
K/Q	0.3985	ambiguous	0.4403	ambiguous	-1.572	Destabilizing	0.83	D	0.789	deleterious	D	0.523887408	None	None	N
K/R	0.1354	likely_benign	0.1273	benign	-0.777	Destabilizing	0.01	N	0.4	neutral	N	0.483059506	None	None	N
K/S	0.9394	likely_pathogenic	0.9501	pathogenic	-2.444	Highly Destabilizing	0.648	D	0.681	prob.neutral	None	None	None	None	N
K/T	0.7568	likely_pathogenic	0.8111	pathogenic	-1.848	Destabilizing	0.83	D	0.775	deleterious	N	0.484433383	None	None	N
K/V	0.7242	likely_pathogenic	0.7535	pathogenic	-0.429	Destabilizing	0.866	D	0.807	deleterious	None	None	None	None	N
K/W	0.959	likely_pathogenic	0.9582	pathogenic	-0.767	Destabilizing	0.993	D	0.833	deleterious	None	None	None	None	N
K/Y	0.876	likely_pathogenic	0.873	pathogenic	-0.41	Destabilizing	0.929	D	0.867	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.