TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27307	82144;82145;82146	chr2:178564213;178564212;178564211	chr2:179428940;179428939;179428938
N2AB	25666	77221;77222;77223	chr2:178564213;178564212;178564211	chr2:179428940;179428939;179428938
N2A	24739	74440;74441;74442	chr2:178564213;178564212;178564211	chr2:179428940;179428939;179428938
N2B	18242	54949;54950;54951	chr2:178564213;178564212;178564211	chr2:179428940;179428939;179428938
Novex-1	18367	55324;55325;55326	chr2:178564213;178564212;178564211	chr2:179428940;179428939;179428938
Novex-2	18434	55525;55526;55527	chr2:178564213;178564212;178564211	chr2:179428940;179428939;179428938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-140
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.2228
• 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/A	rs760826563	-2.015	0.104	D	0.665	0.427	0.619546946635	gnomAD-4.0.0	1.3686E-06	None	None	None	None	N	None	0	0	None	0	2.51953E-05	None	0	0	8.99463E-07	0	0
V/D	None	None	0.667	D	0.868	0.652	0.869592272605	gnomAD-4.0.0	6.843E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99463E-07	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
V/A	0.1523	likely_benign	0.1417	benign	-1.677	Destabilizing	0.104	N	0.665	neutral	D	0.54460069	None	None	N
V/C	0.6072	likely_pathogenic	0.6018	pathogenic	-1.277	Destabilizing	0.968	D	0.763	deleterious	None	None	None	None	N
V/D	0.7036	likely_pathogenic	0.6594	pathogenic	-1.54	Destabilizing	0.667	D	0.868	deleterious	D	0.597846758	None	None	N
V/E	0.62	likely_pathogenic	0.5825	pathogenic	-1.408	Destabilizing	0.726	D	0.841	deleterious	None	None	None	None	N
V/F	0.2038	likely_benign	0.1998	benign	-1.04	Destabilizing	0.124	N	0.789	deleterious	D	0.553221142	None	None	N
V/G	0.3415	ambiguous	0.3111	benign	-2.142	Highly Destabilizing	0.667	D	0.829	deleterious	D	0.581595232	None	None	N
V/H	0.7392	likely_pathogenic	0.7108	pathogenic	-1.759	Destabilizing	0.832	D	0.863	deleterious	None	None	None	None	N
V/I	0.0612	likely_benign	0.0635	benign	-0.44	Destabilizing	None	N	0.223	neutral	N	0.449987948	None	None	N
V/K	0.6288	likely_pathogenic	0.5853	pathogenic	-1.416	Destabilizing	0.567	D	0.844	deleterious	None	None	None	None	N
V/L	0.1702	likely_benign	0.1831	benign	-0.44	Destabilizing	0.009	N	0.501	neutral	D	0.537414304	None	None	N
V/M	0.1237	likely_benign	0.1259	benign	-0.436	Destabilizing	0.567	D	0.681	prob.neutral	None	None	None	None	N
V/N	0.4625	ambiguous	0.434	ambiguous	-1.47	Destabilizing	0.726	D	0.868	deleterious	None	None	None	None	N
V/P	0.7073	likely_pathogenic	0.6743	pathogenic	-0.819	Destabilizing	0.89	D	0.853	deleterious	None	None	None	None	N
V/Q	0.6181	likely_pathogenic	0.5799	pathogenic	-1.415	Destabilizing	0.726	D	0.857	deleterious	None	None	None	None	N
V/R	0.5237	ambiguous	0.4872	ambiguous	-1.155	Destabilizing	0.726	D	0.866	deleterious	None	None	None	None	N
V/S	0.2593	likely_benign	0.2389	benign	-2.127	Highly Destabilizing	0.567	D	0.83	deleterious	None	None	None	None	N
V/T	0.1582	likely_benign	0.1415	benign	-1.848	Destabilizing	0.272	N	0.691	prob.neutral	None	None	None	None	N
V/W	0.825	likely_pathogenic	0.8231	pathogenic	-1.393	Destabilizing	0.909	D	0.856	deleterious	None	None	None	None	N
V/Y	0.5798	likely_pathogenic	0.5888	pathogenic	-1.023	Destabilizing	0.003	N	0.537	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.