TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27447	82564;82565;82566	chr2:178563793;178563792;178563791	chr2:179428520;179428519;179428518
N2AB	25806	77641;77642;77643	chr2:178563793;178563792;178563791	chr2:179428520;179428519;179428518
N2A	24879	74860;74861;74862	chr2:178563793;178563792;178563791	chr2:179428520;179428519;179428518
N2B	18382	55369;55370;55371	chr2:178563793;178563792;178563791	chr2:179428520;179428519;179428518
Novex-1	18507	55744;55745;55746	chr2:178563793;178563792;178563791	chr2:179428520;179428519;179428518
Novex-2	18574	55945;55946;55947	chr2:178563793;178563792;178563791	chr2:179428520;179428519;179428518
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-87
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1727
• 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
V/M	rs758840788	-0.864	0.994	N	0.654	0.425	0.668599470789	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/M	rs758840788	-0.864	0.994	N	0.654	0.425	0.668599470789	gnomAD-4.0.0	4.77417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29849E-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
V/A	0.2594	likely_benign	0.3272	benign	-1.992	Destabilizing	0.892	D	0.455	neutral	N	0.48615272	None	None	N
V/C	0.7875	likely_pathogenic	0.8037	pathogenic	-1.742	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
V/D	0.9214	likely_pathogenic	0.918	pathogenic	-2.88	Highly Destabilizing	0.95	D	0.729	prob.delet.	None	None	None	None	N
V/E	0.591	likely_pathogenic	0.5815	pathogenic	-2.713	Highly Destabilizing	0.056	N	0.398	neutral	N	0.475371104	None	None	N
V/F	0.4923	ambiguous	0.5087	ambiguous	-1.271	Destabilizing	0.996	D	0.801	deleterious	None	None	None	None	N
V/G	0.5529	ambiguous	0.5906	pathogenic	-2.448	Highly Destabilizing	0.967	D	0.738	prob.delet.	N	0.516729371	None	None	N
V/H	0.8889	likely_pathogenic	0.8971	pathogenic	-2.191	Highly Destabilizing	0.997	D	0.81	deleterious	None	None	None	None	N
V/I	0.1194	likely_benign	0.1155	benign	-0.741	Destabilizing	0.901	D	0.481	neutral	None	None	None	None	N
V/K	0.6368	likely_pathogenic	0.6468	pathogenic	-1.586	Destabilizing	0.95	D	0.685	prob.neutral	None	None	None	None	N
V/L	0.5911	likely_pathogenic	0.5807	pathogenic	-0.741	Destabilizing	0.773	D	0.469	neutral	N	0.490214417	None	None	N
V/M	0.2749	likely_benign	0.2704	benign	-0.916	Destabilizing	0.994	D	0.654	neutral	N	0.503144566	None	None	N
V/N	0.7963	likely_pathogenic	0.7937	pathogenic	-1.869	Destabilizing	0.975	D	0.829	deleterious	None	None	None	None	N
V/P	0.9889	likely_pathogenic	0.9922	pathogenic	-1.132	Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	N
V/Q	0.517	ambiguous	0.5272	ambiguous	-1.807	Destabilizing	0.95	D	0.772	deleterious	None	None	None	None	N
V/R	0.5666	likely_pathogenic	0.5913	pathogenic	-1.341	Destabilizing	0.975	D	0.83	deleterious	None	None	None	None	N
V/S	0.4573	ambiguous	0.5115	ambiguous	-2.39	Highly Destabilizing	0.975	D	0.685	prob.neutral	None	None	None	None	N
V/T	0.4086	ambiguous	0.4174	ambiguous	-2.102	Highly Destabilizing	0.916	D	0.522	neutral	None	None	None	None	N
V/W	0.974	likely_pathogenic	0.9765	pathogenic	-1.774	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
V/Y	0.8685	likely_pathogenic	0.8781	pathogenic	-1.413	Destabilizing	0.996	D	0.801	deleterious	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.