TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24596	74011;74012;74013	chr2:178572346;178572345;178572344	chr2:179437073;179437072;179437071
N2AB	22955	69088;69089;69090	chr2:178572346;178572345;178572344	chr2:179437073;179437072;179437071
N2A	22028	66307;66308;66309	chr2:178572346;178572345;178572344	chr2:179437073;179437072;179437071
N2B	15531	46816;46817;46818	chr2:178572346;178572345;178572344	chr2:179437073;179437072;179437071
Novex-1	15656	47191;47192;47193	chr2:178572346;178572345;178572344	chr2:179437073;179437072;179437071
Novex-2	15723	47392;47393;47394	chr2:178572346;178572345;178572344	chr2:179437073;179437072;179437071
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-66
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.1937
• 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
E/A	None	None	0.997	N	0.676	0.472	0.362758974969	gnomAD-4.0.0	1.59586E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86979E-06	0	0
E/K	rs758107705	None	0.998	N	0.543	0.36	0.385249989106	gnomAD-4.0.0	2.74019E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60236E-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
E/A	0.5187	ambiguous	0.4464	ambiguous	-1.002	Destabilizing	0.997	D	0.676	prob.neutral	N	0.481684679	None	None	N
E/C	0.9202	likely_pathogenic	0.9029	pathogenic	-0.755	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
E/D	0.8971	likely_pathogenic	0.8437	pathogenic	-1.581	Destabilizing	0.974	D	0.488	neutral	D	0.524035708	None	None	N
E/F	0.978	likely_pathogenic	0.9693	pathogenic	-1.113	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
E/G	0.7597	likely_pathogenic	0.6566	pathogenic	-1.352	Destabilizing	1.0	D	0.764	deleterious	N	0.508893968	None	None	N
E/H	0.9499	likely_pathogenic	0.9244	pathogenic	-1.337	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/I	0.6567	likely_pathogenic	0.6417	pathogenic	-0.043	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
E/K	0.6642	likely_pathogenic	0.5611	ambiguous	-1.073	Destabilizing	0.998	D	0.543	neutral	N	0.480723627	None	None	N
E/L	0.892	likely_pathogenic	0.8491	pathogenic	-0.043	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
E/M	0.7746	likely_pathogenic	0.7336	pathogenic	0.517	Stabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
E/N	0.9128	likely_pathogenic	0.873	pathogenic	-1.343	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
E/P	0.9982	likely_pathogenic	0.9977	pathogenic	-0.343	Destabilizing	0.994	D	0.813	deleterious	None	None	None	None	N
E/Q	0.3397	likely_benign	0.2793	benign	-1.178	Destabilizing	0.999	D	0.621	neutral	N	0.487040276	None	None	N
E/R	0.7986	likely_pathogenic	0.7212	pathogenic	-1.009	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.6856	likely_pathogenic	0.6144	pathogenic	-1.819	Destabilizing	0.997	D	0.581	neutral	None	None	None	None	N
E/T	0.7215	likely_pathogenic	0.6643	pathogenic	-1.504	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
E/V	0.3759	ambiguous	0.3485	ambiguous	-0.343	Destabilizing	0.998	D	0.829	deleterious	N	0.440492447	None	None	N
E/W	0.9959	likely_pathogenic	0.9935	pathogenic	-1.205	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
E/Y	0.9748	likely_pathogenic	0.9624	pathogenic	-0.927	Destabilizing	1.0	D	0.858	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.