TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2312	7159;7160;7161	chr2:178774330;178774329;178774328	chr2:179639057;179639056;179639055
N2AB	2312	7159;7160;7161	chr2:178774330;178774329;178774328	chr2:179639057;179639056;179639055
N2A	2312	7159;7160;7161	chr2:178774330;178774329;178774328	chr2:179639057;179639056;179639055
N2B	2266	7021;7022;7023	chr2:178774330;178774329;178774328	chr2:179639057;179639056;179639055
Novex-1	2266	7021;7022;7023	chr2:178774330;178774329;178774328	chr2:179639057;179639056;179639055
Novex-2	2266	7021;7022;7023	chr2:178774330;178774329;178774328	chr2:179639057;179639056;179639055
Novex-3	2312	7159;7160;7161	chr2:178774330;178774329;178774328	chr2:179639057;179639056;179639055

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-12
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.2387
• 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
Y/C	None	None	0.999	N	0.752	0.756	0.7168682315	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
Y/H	None	None	0.046	N	0.351	0.428	0.335164054921	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
Y/A	0.9307	likely_pathogenic	0.9409	pathogenic	-2.961	Highly Destabilizing	0.953	D	0.626	neutral	None	None	None	None	N
Y/C	0.4034	ambiguous	0.4272	ambiguous	-2.284	Highly Destabilizing	0.999	D	0.752	deleterious	N	0.508651577	None	None	N
Y/D	0.9297	likely_pathogenic	0.9412	pathogenic	-3.008	Highly Destabilizing	0.982	D	0.785	deleterious	D	0.545178927	None	None	N
Y/E	0.9662	likely_pathogenic	0.9716	pathogenic	-2.833	Highly Destabilizing	0.986	D	0.685	prob.neutral	None	None	None	None	N
Y/F	0.1527	likely_benign	0.158	benign	-1.218	Destabilizing	0.969	D	0.528	neutral	N	0.487269977	None	None	N
Y/G	0.9246	likely_pathogenic	0.9345	pathogenic	-3.385	Highly Destabilizing	0.986	D	0.739	prob.delet.	None	None	None	None	N
Y/H	0.4442	ambiguous	0.4826	ambiguous	-2.049	Highly Destabilizing	0.046	N	0.351	neutral	N	0.504009717	None	None	N
Y/I	0.7325	likely_pathogenic	0.7417	pathogenic	-1.583	Destabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
Y/K	0.9384	likely_pathogenic	0.9477	pathogenic	-2.192	Highly Destabilizing	0.986	D	0.725	prob.delet.	None	None	None	None	N
Y/L	0.7776	likely_pathogenic	0.7915	pathogenic	-1.583	Destabilizing	0.953	D	0.623	neutral	None	None	None	None	N
Y/M	0.8521	likely_pathogenic	0.8667	pathogenic	-1.511	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
Y/N	0.6214	likely_pathogenic	0.6576	pathogenic	-2.881	Highly Destabilizing	0.982	D	0.723	prob.delet.	D	0.544766555	None	None	N
Y/P	0.9952	likely_pathogenic	0.9956	pathogenic	-2.052	Highly Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
Y/Q	0.9115	likely_pathogenic	0.9254	pathogenic	-2.664	Highly Destabilizing	0.986	D	0.737	prob.delet.	None	None	None	None	N
Y/R	0.8664	likely_pathogenic	0.8831	pathogenic	-1.879	Destabilizing	0.986	D	0.756	deleterious	None	None	None	None	N
Y/S	0.8144	likely_pathogenic	0.8399	pathogenic	-3.346	Highly Destabilizing	0.982	D	0.688	prob.neutral	D	0.54287588	None	None	N
Y/T	0.8535	likely_pathogenic	0.8793	pathogenic	-3.042	Highly Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
Y/V	0.6573	likely_pathogenic	0.6765	pathogenic	-2.052	Highly Destabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	N
Y/W	0.6409	likely_pathogenic	0.6633	pathogenic	-0.68	Destabilizing	0.999	D	0.645	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.