TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32572	97939;97940;97941	chr2:178541363;178541362;178541361	chr2:179406090;179406089;179406088
N2AB	30931	93016;93017;93018	chr2:178541363;178541362;178541361	chr2:179406090;179406089;179406088
N2A	30004	90235;90236;90237	chr2:178541363;178541362;178541361	chr2:179406090;179406089;179406088
N2B	23507	70744;70745;70746	chr2:178541363;178541362;178541361	chr2:179406090;179406089;179406088
Novex-1	23632	71119;71120;71121	chr2:178541363;178541362;178541361	chr2:179406090;179406089;179406088
Novex-2	23699	71320;71321;71322	chr2:178541363;178541362;178541361	chr2:179406090;179406089;179406088
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-125
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.21
• 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
H/Q	None	None	0.996	N	0.739	0.356	0.330589388543	gnomAD-4.0.0	1.38141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81102E-06	0	0
H/Y	None	None	0.061	N	0.282	0.221	0.163833314356	gnomAD-4.0.0	1.62164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.47697E-05	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
H/A	0.9653	likely_pathogenic	0.9723	pathogenic	-2.215	Highly Destabilizing	0.969	D	0.799	deleterious	None	None	None	None	N
H/C	0.491	ambiguous	0.482	ambiguous	-1.145	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
H/D	0.9464	likely_pathogenic	0.9608	pathogenic	-2.078	Highly Destabilizing	0.996	D	0.791	deleterious	N	0.448504215	None	None	N
H/E	0.9618	likely_pathogenic	0.969	pathogenic	-1.859	Destabilizing	0.99	D	0.723	prob.delet.	None	None	None	None	N
H/F	0.2958	likely_benign	0.241	benign	-0.166	Destabilizing	0.046	N	0.605	neutral	None	None	None	None	N
H/G	0.9695	likely_pathogenic	0.9767	pathogenic	-2.646	Highly Destabilizing	0.99	D	0.801	deleterious	None	None	None	None	N
H/I	0.8067	likely_pathogenic	0.8243	pathogenic	-0.907	Destabilizing	0.982	D	0.814	deleterious	None	None	None	None	N
H/K	0.9813	likely_pathogenic	0.9845	pathogenic	-1.331	Destabilizing	0.991	D	0.781	deleterious	None	None	None	None	N
H/L	0.5106	ambiguous	0.5326	ambiguous	-0.907	Destabilizing	0.852	D	0.815	deleterious	N	0.375985182	None	None	N
H/M	0.8161	likely_pathogenic	0.83	pathogenic	-0.985	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
H/N	0.6057	likely_pathogenic	0.6899	pathogenic	-2.184	Highly Destabilizing	0.986	D	0.72	prob.delet.	N	0.467089976	None	None	N
H/P	0.9739	likely_pathogenic	0.982	pathogenic	-1.338	Destabilizing	0.996	D	0.836	deleterious	N	0.467089976	None	None	N
H/Q	0.8866	likely_pathogenic	0.9011	pathogenic	-1.775	Destabilizing	0.996	D	0.739	prob.delet.	N	0.467089976	None	None	N
H/R	0.9413	likely_pathogenic	0.9507	pathogenic	-1.422	Destabilizing	0.988	D	0.743	deleterious	N	0.467089976	None	None	N
H/S	0.9135	likely_pathogenic	0.9323	pathogenic	-2.347	Highly Destabilizing	0.969	D	0.765	deleterious	None	None	None	None	N
H/T	0.9467	likely_pathogenic	0.9618	pathogenic	-2.006	Highly Destabilizing	0.991	D	0.818	deleterious	None	None	None	None	N
H/V	0.8174	likely_pathogenic	0.8361	pathogenic	-1.338	Destabilizing	0.939	D	0.815	deleterious	None	None	None	None	N
H/W	0.5936	likely_pathogenic	0.5244	ambiguous	0.543	Stabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
H/Y	0.1073	likely_benign	0.0867	benign	0.221	Stabilizing	0.061	N	0.282	neutral	N	0.320057329	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.