TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24550	73873;73874;73875	chr2:178572484;178572483;178572482	chr2:179437211;179437210;179437209
N2AB	22909	68950;68951;68952	chr2:178572484;178572483;178572482	chr2:179437211;179437210;179437209
N2A	21982	66169;66170;66171	chr2:178572484;178572483;178572482	chr2:179437211;179437210;179437209
N2B	15485	46678;46679;46680	chr2:178572484;178572483;178572482	chr2:179437211;179437210;179437209
Novex-1	15610	47053;47054;47055	chr2:178572484;178572483;178572482	chr2:179437211;179437210;179437209
Novex-2	15677	47254;47255;47256	chr2:178572484;178572483;178572482	chr2:179437211;179437210;179437209
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-66
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7199
• Predicted PPI site: I

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
K/E	rs1323106581	None	0.002	N	0.143	0.184	0.223847106136	gnomAD-4.0.0	1.36906E-06	None	None	None	None	I	None	0	2.23774E-05	None	0	0	None	0	0	0	0	1.65722E-05

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
K/A	0.7295	likely_pathogenic	0.6174	pathogenic	-0.048	Destabilizing	0.757	D	0.543	neutral	None	None	None	None	I
K/C	0.8818	likely_pathogenic	0.83	pathogenic	-0.18	Destabilizing	0.996	D	0.688	prob.neutral	None	None	None	None	I
K/D	0.9294	likely_pathogenic	0.8855	pathogenic	0.107	Stabilizing	0.609	D	0.569	neutral	None	None	None	None	I
K/E	0.708	likely_pathogenic	0.5677	pathogenic	0.132	Stabilizing	0.002	N	0.143	neutral	N	0.455024756	None	None	I
K/F	0.9695	likely_pathogenic	0.9511	pathogenic	-0.135	Destabilizing	0.964	D	0.657	neutral	None	None	None	None	I
K/G	0.8604	likely_pathogenic	0.7703	pathogenic	-0.286	Destabilizing	0.757	D	0.603	neutral	None	None	None	None	I
K/H	0.5845	likely_pathogenic	0.4867	ambiguous	-0.567	Destabilizing	0.902	D	0.572	neutral	None	None	None	None	I
K/I	0.7726	likely_pathogenic	0.7012	pathogenic	0.508	Stabilizing	0.329	N	0.664	neutral	N	0.519289665	None	None	I
K/L	0.76	likely_pathogenic	0.6758	pathogenic	0.508	Stabilizing	0.084	N	0.587	neutral	None	None	None	None	I
K/M	0.7071	likely_pathogenic	0.6095	pathogenic	0.287	Stabilizing	0.968	D	0.568	neutral	None	None	None	None	I
K/N	0.8738	likely_pathogenic	0.8117	pathogenic	0.197	Stabilizing	0.701	D	0.485	neutral	N	0.517422796	None	None	I
K/P	0.7058	likely_pathogenic	0.6132	pathogenic	0.352	Stabilizing	0.957	D	0.584	neutral	None	None	None	None	I
K/Q	0.3838	ambiguous	0.3009	benign	0.038	Stabilizing	0.125	N	0.536	neutral	N	0.518692232	None	None	I
K/R	0.0786	likely_benign	0.0732	benign	-0.093	Destabilizing	0.001	N	0.081	neutral	N	0.464975178	None	None	I
K/S	0.8604	likely_pathogenic	0.7801	pathogenic	-0.324	Destabilizing	0.757	D	0.504	neutral	None	None	None	None	I
K/T	0.6548	likely_pathogenic	0.5432	ambiguous	-0.137	Destabilizing	0.413	N	0.577	neutral	N	0.508552597	None	None	I
K/V	0.6778	likely_pathogenic	0.5911	pathogenic	0.352	Stabilizing	0.461	N	0.555	neutral	None	None	None	None	I
K/W	0.946	likely_pathogenic	0.9165	pathogenic	-0.117	Destabilizing	0.997	D	0.731	prob.delet.	None	None	None	None	I
K/Y	0.9116	likely_pathogenic	0.8766	pathogenic	0.217	Stabilizing	0.758	D	0.649	neutral	None	None	None	None	I

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.