TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5910	17953;17954;17955	chr2:178730937;178730936;178730935	chr2:179595664;179595663;179595662
N2AB	5593	17002;17003;17004	chr2:178730937;178730936;178730935	chr2:179595664;179595663;179595662
N2A	4666	14221;14222;14223	chr2:178730937;178730936;178730935	chr2:179595664;179595663;179595662
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-42
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1382
• 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
I/V	rs1311857097	-1.659	0.011	N	0.217	0.088	0.258283824007	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.8E-05	0	0
I/V	rs1311857097	-1.659	0.011	N	0.217	0.088	0.258283824007	gnomAD-4.0.0	1.29226E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.5219E-04	0	0	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
I/A	0.9345	likely_pathogenic	0.9415	pathogenic	-2.903	Highly Destabilizing	0.702	D	0.747	deleterious	None	None	None	None	N
I/C	0.9386	likely_pathogenic	0.9467	pathogenic	-2.441	Highly Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
I/D	0.9968	likely_pathogenic	0.998	pathogenic	-3.03	Highly Destabilizing	0.996	D	0.889	deleterious	None	None	None	None	N
I/E	0.9884	likely_pathogenic	0.9916	pathogenic	-2.803	Highly Destabilizing	0.988	D	0.888	deleterious	None	None	None	None	N
I/F	0.4922	ambiguous	0.4993	ambiguous	-1.803	Destabilizing	0.968	D	0.785	deleterious	N	0.467100258	None	None	N
I/G	0.9846	likely_pathogenic	0.9886	pathogenic	-3.461	Highly Destabilizing	0.988	D	0.877	deleterious	None	None	None	None	N
I/H	0.9872	likely_pathogenic	0.9908	pathogenic	-2.719	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
I/K	0.9772	likely_pathogenic	0.9812	pathogenic	-2.221	Highly Destabilizing	0.988	D	0.886	deleterious	None	None	None	None	N
I/L	0.1381	likely_benign	0.1389	benign	-1.282	Destabilizing	0.011	N	0.287	neutral	N	0.301942344	None	None	N
I/M	0.1864	likely_benign	0.1624	benign	-1.353	Destabilizing	0.968	D	0.76	deleterious	N	0.485859377	None	None	N
I/N	0.9595	likely_pathogenic	0.9733	pathogenic	-2.582	Highly Destabilizing	0.995	D	0.863	deleterious	N	0.50540793	None	None	N
I/P	0.9917	likely_pathogenic	0.9942	pathogenic	-1.804	Destabilizing	0.996	D	0.878	deleterious	None	None	None	None	N
I/Q	0.9802	likely_pathogenic	0.9838	pathogenic	-2.464	Highly Destabilizing	0.996	D	0.88	deleterious	None	None	None	None	N
I/R	0.9697	likely_pathogenic	0.9773	pathogenic	-1.852	Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
I/S	0.9667	likely_pathogenic	0.9755	pathogenic	-3.371	Highly Destabilizing	0.984	D	0.861	deleterious	N	0.505234572	None	None	N
I/T	0.9408	likely_pathogenic	0.9524	pathogenic	-2.989	Highly Destabilizing	0.896	D	0.805	deleterious	N	0.505234572	None	None	N
I/V	0.1171	likely_benign	0.1134	benign	-1.804	Destabilizing	0.011	N	0.217	neutral	N	0.367469195	None	None	N
I/W	0.9735	likely_pathogenic	0.9763	pathogenic	-2.085	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
I/Y	0.9205	likely_pathogenic	0.9331	pathogenic	-1.876	Destabilizing	0.996	D	0.821	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.