TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31719	95380;95381;95382	chr2:178546081;178546080;178546079	chr2:179410808;179410807;179410806
N2AB	30078	90457;90458;90459	chr2:178546081;178546080;178546079	chr2:179410808;179410807;179410806
N2A	29151	87676;87677;87678	chr2:178546081;178546080;178546079	chr2:179410808;179410807;179410806
N2B	22654	68185;68186;68187	chr2:178546081;178546080;178546079	chr2:179410808;179410807;179410806
Novex-1	22779	68560;68561;68562	chr2:178546081;178546080;178546079	chr2:179410808;179410807;179410806
Novex-2	22846	68761;68762;68763	chr2:178546081;178546080;178546079	chr2:179410808;179410807;179410806
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-119
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4563
• 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
R/K	None	None	0.997	N	0.538	0.307	0.29385284311	gnomAD-4.0.0	1.5955E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86781E-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
R/A	0.4426	ambiguous	0.5376	ambiguous	-0.064	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
R/C	0.3055	likely_benign	0.3659	ambiguous	-0.244	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
R/D	0.6437	likely_pathogenic	0.717	pathogenic	-0.065	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
R/E	0.4735	ambiguous	0.5411	ambiguous	-0.012	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
R/F	0.6952	likely_pathogenic	0.7741	pathogenic	-0.332	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
R/G	0.2456	likely_benign	0.3141	benign	-0.24	Destabilizing	1.0	D	0.599	neutral	N	0.368080562	None	None	N
R/H	0.1396	likely_benign	0.1624	benign	-0.641	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
R/I	0.5482	ambiguous	0.6268	pathogenic	0.358	Stabilizing	1.0	D	0.704	prob.neutral	N	0.496143447	None	None	N
R/K	0.152	likely_benign	0.1711	benign	-0.117	Destabilizing	0.997	D	0.538	neutral	N	0.441500885	None	None	N
R/L	0.3879	ambiguous	0.4667	ambiguous	0.358	Stabilizing	1.0	D	0.599	neutral	None	None	None	None	N
R/M	0.4299	ambiguous	0.5021	ambiguous	-0.01	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
R/N	0.5442	ambiguous	0.6166	pathogenic	0.093	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
R/P	0.8154	likely_pathogenic	0.8836	pathogenic	0.237	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
R/Q	0.1487	likely_benign	0.1718	benign	-0.026	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
R/S	0.4893	ambiguous	0.5802	pathogenic	-0.285	Destabilizing	1.0	D	0.679	prob.neutral	N	0.407790957	None	None	N
R/T	0.3555	ambiguous	0.4364	ambiguous	-0.104	Destabilizing	1.0	D	0.665	neutral	N	0.467359335	None	None	N
R/V	0.5561	ambiguous	0.6482	pathogenic	0.237	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
R/W	0.299	likely_benign	0.3781	ambiguous	-0.389	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
R/Y	0.5185	ambiguous	0.5928	pathogenic	0.022	Stabilizing	1.0	D	0.685	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.