TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27293	82102;82103;82104	chr2:178564255;178564254;178564253	chr2:179428982;179428981;179428980
N2AB	25652	77179;77180;77181	chr2:178564255;178564254;178564253	chr2:179428982;179428981;179428980
N2A	24725	74398;74399;74400	chr2:178564255;178564254;178564253	chr2:179428982;179428981;179428980
N2B	18228	54907;54908;54909	chr2:178564255;178564254;178564253	chr2:179428982;179428981;179428980
Novex-1	18353	55282;55283;55284	chr2:178564255;178564254;178564253	chr2:179428982;179428981;179428980
Novex-2	18420	55483;55484;55485	chr2:178564255;178564254;178564253	chr2:179428982;179428981;179428980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-140
• Domain position: 16
• Structural Position: 28
• Q(SASA): 0.2929
• Predicted PPI site: I

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
F/L	None	None	0.999	N	0.567	0.42	0.395143324098	gnomAD-4.0.0	6.84439E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-05	0
F/S	rs751553517	-2.276	1.0	N	0.751	0.557	0.680157959374	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
F/S	rs751553517	-2.276	1.0	N	0.751	0.557	0.680157959374	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-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
F/A	0.8611	likely_pathogenic	0.864	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
F/C	0.5888	likely_pathogenic	0.574	pathogenic	-2.15	Highly Destabilizing	1.0	D	0.751	deleterious	N	0.455843472	None	None	I
F/D	0.9975	likely_pathogenic	0.9981	pathogenic	-3.198	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
F/E	0.9967	likely_pathogenic	0.9972	pathogenic	-2.99	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
F/G	0.9813	likely_pathogenic	0.9823	pathogenic	-3.188	Highly Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
F/H	0.9755	likely_pathogenic	0.9802	pathogenic	-1.735	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
F/I	0.2649	likely_benign	0.2837	benign	-1.296	Destabilizing	1.0	D	0.732	prob.delet.	N	0.416879295	None	None	I
F/K	0.9961	likely_pathogenic	0.9969	pathogenic	-2.558	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
F/L	0.7883	likely_pathogenic	0.8044	pathogenic	-1.296	Destabilizing	0.999	D	0.567	neutral	N	0.40337128	None	None	I
F/M	0.5686	likely_pathogenic	0.5977	pathogenic	-1.053	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
F/N	0.9913	likely_pathogenic	0.9925	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
F/P	0.9984	likely_pathogenic	0.9987	pathogenic	-1.788	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
F/Q	0.9932	likely_pathogenic	0.9941	pathogenic	-2.996	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
F/R	0.9879	likely_pathogenic	0.9898	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
F/S	0.9485	likely_pathogenic	0.9494	pathogenic	-3.726	Highly Destabilizing	1.0	D	0.751	deleterious	N	0.466946288	None	None	I
F/T	0.9043	likely_pathogenic	0.9134	pathogenic	-3.395	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
F/V	0.2565	likely_benign	0.2776	benign	-1.788	Destabilizing	1.0	D	0.729	prob.delet.	N	0.429400301	None	None	I
F/W	0.8458	likely_pathogenic	0.8579	pathogenic	-0.496	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
F/Y	0.5704	likely_pathogenic	0.5971	pathogenic	-0.875	Destabilizing	0.999	D	0.584	neutral	N	0.455589982	None	None	I

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.