TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28591	85996;85997;85998	chr2:178560361;178560360;178560359	chr2:179425088;179425087;179425086
N2AB	26950	81073;81074;81075	chr2:178560361;178560360;178560359	chr2:179425088;179425087;179425086
N2A	26023	78292;78293;78294	chr2:178560361;178560360;178560359	chr2:179425088;179425087;179425086
N2B	19526	58801;58802;58803	chr2:178560361;178560360;178560359	chr2:179425088;179425087;179425086
Novex-1	19651	59176;59177;59178	chr2:178560361;178560360;178560359	chr2:179425088;179425087;179425086
Novex-2	19718	59377;59378;59379	chr2:178560361;178560360;178560359	chr2:179425088;179425087;179425086
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-96
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.182
• 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/K	None	None	0.999	N	0.592	0.378	0.453307948783	gnomAD-4.0.0	2.737E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59789E-06	0	0
E/Q	rs556819067	None	1.0	N	0.619	0.259	0.329020015101	gnomAD-4.0.0	6.84251E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99473E-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
E/A	0.7659	likely_pathogenic	0.7159	pathogenic	-1.014	Destabilizing	0.999	D	0.673	neutral	N	0.467965424	None	None	N
E/C	0.9828	likely_pathogenic	0.9778	pathogenic	-0.529	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.4871	ambiguous	0.4222	ambiguous	-1.204	Destabilizing	0.999	D	0.492	neutral	N	0.410276688	None	None	N
E/F	0.9861	likely_pathogenic	0.9781	pathogenic	-0.507	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/G	0.6859	likely_pathogenic	0.6063	pathogenic	-1.38	Destabilizing	1.0	D	0.713	prob.delet.	N	0.474410659	None	None	N
E/H	0.9482	likely_pathogenic	0.9287	pathogenic	-0.79	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/I	0.9291	likely_pathogenic	0.8893	pathogenic	-0.011	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/K	0.7914	likely_pathogenic	0.7372	pathogenic	-0.75	Destabilizing	0.999	D	0.592	neutral	N	0.493815218	None	None	N
E/L	0.8978	likely_pathogenic	0.8504	pathogenic	-0.011	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/M	0.9187	likely_pathogenic	0.8845	pathogenic	0.503	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/N	0.8708	likely_pathogenic	0.8227	pathogenic	-1.174	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/P	0.9717	likely_pathogenic	0.9567	pathogenic	-0.324	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Q	0.5315	ambiguous	0.4701	ambiguous	-1.056	Destabilizing	1.0	D	0.619	neutral	N	0.484926376	None	None	N
E/R	0.8643	likely_pathogenic	0.8282	pathogenic	-0.467	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
E/S	0.832	likely_pathogenic	0.7795	pathogenic	-1.519	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
E/T	0.9056	likely_pathogenic	0.8611	pathogenic	-1.217	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/V	0.8384	likely_pathogenic	0.7642	pathogenic	-0.324	Destabilizing	1.0	D	0.798	deleterious	N	0.485931548	None	None	N
E/W	0.9935	likely_pathogenic	0.9898	pathogenic	-0.252	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/Y	0.9745	likely_pathogenic	0.9604	pathogenic	-0.253	Destabilizing	1.0	D	0.799	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.