TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32460	97603;97604;97605	chr2:178542378;178542377;178542376	chr2:179407105;179407104;179407103
N2AB	30819	92680;92681;92682	chr2:178542378;178542377;178542376	chr2:179407105;179407104;179407103
N2A	29892	89899;89900;89901	chr2:178542378;178542377;178542376	chr2:179407105;179407104;179407103
N2B	23395	70408;70409;70410	chr2:178542378;178542377;178542376	chr2:179407105;179407104;179407103
Novex-1	23520	70783;70784;70785	chr2:178542378;178542377;178542376	chr2:179407105;179407104;179407103
Novex-2	23587	70984;70985;70986	chr2:178542378;178542377;178542376	chr2:179407105;179407104;179407103
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-124
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.562
• 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
K/E	rs965156924	None	0.996	N	0.538	0.344	0.292787519742	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	1.69E-04	0	0	0	0	None	0	0	0	0	0
K/E	rs965156924	None	0.996	N	0.538	0.344	0.292787519742	gnomAD-4.0.0	4.60254E-05	None	None	None	None	N	None	1.69E-04	0	None	0	0	None	0	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
K/A	0.8933	likely_pathogenic	0.8653	pathogenic	-0.797	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
K/C	0.8765	likely_pathogenic	0.8245	pathogenic	-0.836	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/D	0.9768	likely_pathogenic	0.9708	pathogenic	0.048	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/E	0.8793	likely_pathogenic	0.8429	pathogenic	0.173	Stabilizing	0.996	D	0.538	neutral	N	0.479318049	None	None	N
K/F	0.9812	likely_pathogenic	0.9738	pathogenic	-0.545	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/G	0.94	likely_pathogenic	0.9218	pathogenic	-1.157	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/H	0.5579	ambiguous	0.4919	ambiguous	-1.413	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
K/I	0.8255	likely_pathogenic	0.7918	pathogenic	0.136	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/L	0.8298	likely_pathogenic	0.789	pathogenic	0.136	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/M	0.7683	likely_pathogenic	0.7247	pathogenic	0.009	Stabilizing	1.0	D	0.696	prob.neutral	N	0.498943241	None	None	N
K/N	0.9366	likely_pathogenic	0.9179	pathogenic	-0.493	Destabilizing	0.999	D	0.683	prob.neutral	D	0.522385899	None	None	N
K/P	0.9607	likely_pathogenic	0.9487	pathogenic	-0.146	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/Q	0.4709	ambiguous	0.4155	ambiguous	-0.558	Destabilizing	0.999	D	0.677	prob.neutral	N	0.489788981	None	None	N
K/R	0.0912	likely_benign	0.0858	benign	-0.493	Destabilizing	0.64	D	0.275	neutral	N	0.492025706	None	None	N
K/S	0.9066	likely_pathogenic	0.8824	pathogenic	-1.263	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	N
K/T	0.6232	likely_pathogenic	0.5862	pathogenic	-0.917	Destabilizing	0.999	D	0.748	deleterious	N	0.480186986	None	None	N
K/V	0.7837	likely_pathogenic	0.7465	pathogenic	-0.146	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/W	0.9588	likely_pathogenic	0.9364	pathogenic	-0.36	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/Y	0.9242	likely_pathogenic	0.9026	pathogenic	-0.067	Destabilizing	1.0	D	0.702	prob.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.