TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17790	53593;53594;53595	chr2:178607234;178607233;178607232	chr2:179471961;179471960;179471959
N2AB	16149	48670;48671;48672	chr2:178607234;178607233;178607232	chr2:179471961;179471960;179471959
N2A	15222	45889;45890;45891	chr2:178607234;178607233;178607232	chr2:179471961;179471960;179471959
N2B	8725	26398;26399;26400	chr2:178607234;178607233;178607232	chr2:179471961;179471960;179471959
Novex-1	8850	26773;26774;26775	chr2:178607234;178607233;178607232	chr2:179471961;179471960;179471959
Novex-2	8917	26974;26975;26976	chr2:178607234;178607233;178607232	chr2:179471961;179471960;179471959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-17
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5921
• 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
D/G	None	None	1.0	N	0.682	0.533	0.429435026966	gnomAD-4.0.0	2.05361E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69935E-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
D/A	0.9049	likely_pathogenic	0.7905	pathogenic	-0.202	Destabilizing	1.0	D	0.729	prob.delet.	N	0.479558311	None	None	I
D/C	0.9764	likely_pathogenic	0.9508	pathogenic	0.189	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
D/E	0.7973	likely_pathogenic	0.6877	pathogenic	-0.313	Destabilizing	1.0	D	0.375	neutral	N	0.467695027	None	None	I
D/F	0.9586	likely_pathogenic	0.896	pathogenic	-0.339	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
D/G	0.8825	likely_pathogenic	0.7694	pathogenic	-0.378	Destabilizing	1.0	D	0.682	prob.neutral	N	0.489775755	None	None	I
D/H	0.9333	likely_pathogenic	0.8493	pathogenic	-0.266	Destabilizing	1.0	D	0.623	neutral	N	0.475292351	None	None	I
D/I	0.8936	likely_pathogenic	0.8296	pathogenic	0.203	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
D/K	0.9602	likely_pathogenic	0.9168	pathogenic	0.315	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/L	0.9274	likely_pathogenic	0.877	pathogenic	0.203	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
D/M	0.9658	likely_pathogenic	0.9416	pathogenic	0.405	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/N	0.4569	ambiguous	0.3759	ambiguous	0.165	Stabilizing	1.0	D	0.629	neutral	N	0.490022764	None	None	I
D/P	0.9964	likely_pathogenic	0.9941	pathogenic	0.09	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
D/Q	0.9574	likely_pathogenic	0.9119	pathogenic	0.177	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
D/R	0.9701	likely_pathogenic	0.9336	pathogenic	0.388	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
D/S	0.8139	likely_pathogenic	0.6611	pathogenic	0.053	Stabilizing	1.0	D	0.658	neutral	None	None	None	None	I
D/T	0.8585	likely_pathogenic	0.8073	pathogenic	0.182	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
D/V	0.8091	likely_pathogenic	0.6903	pathogenic	0.09	Stabilizing	1.0	D	0.751	deleterious	N	0.483672915	None	None	I
D/W	0.9925	likely_pathogenic	0.9815	pathogenic	-0.285	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
D/Y	0.8212	likely_pathogenic	0.589	pathogenic	-0.124	Destabilizing	1.0	D	0.667	neutral	N	0.507224445	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.