TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25694	77305;77306;77307	chr2:178569052;178569051;178569050	chr2:179433779;179433778;179433777
N2AB	24053	72382;72383;72384	chr2:178569052;178569051;178569050	chr2:179433779;179433778;179433777
N2A	23126	69601;69602;69603	chr2:178569052;178569051;178569050	chr2:179433779;179433778;179433777
N2B	16629	50110;50111;50112	chr2:178569052;178569051;178569050	chr2:179433779;179433778;179433777
Novex-1	16754	50485;50486;50487	chr2:178569052;178569051;178569050	chr2:179433779;179433778;179433777
Novex-2	16821	50686;50687;50688	chr2:178569052;178569051;178569050	chr2:179433779;179433778;179433777
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: Fn3-74
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.6671
• 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/N	rs757757476	0.207	0.999	N	0.806	0.176	0.149567049428	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/N	rs757757476	0.207	0.999	N	0.806	0.176	0.149567049428	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43402E-05	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	0.7113	likely_pathogenic	0.7322	pathogenic	-0.132	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
K/C	0.8471	likely_pathogenic	0.8539	pathogenic	-0.354	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/D	0.9473	likely_pathogenic	0.9529	pathogenic	0.347	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/E	0.6763	likely_pathogenic	0.6875	pathogenic	0.382	Stabilizing	0.994	D	0.764	deleterious	N	0.460525323	None	None	N
K/F	0.9269	likely_pathogenic	0.935	pathogenic	-0.243	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/G	0.8969	likely_pathogenic	0.9065	pathogenic	-0.37	Destabilizing	1.0	D	0.689	prob.delet.	None	None	None	None	N
K/H	0.5397	ambiguous	0.5657	pathogenic	-0.633	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/I	0.5105	ambiguous	0.5123	ambiguous	0.422	Stabilizing	0.987	D	0.797	deleterious	None	None	None	None	N
K/L	0.5108	ambiguous	0.5269	ambiguous	0.422	Stabilizing	0.987	D	0.689	prob.delet.	None	None	None	None	N
K/M	0.4207	ambiguous	0.4288	ambiguous	0.205	Stabilizing	0.999	D	0.777	deleterious	N	0.465867694	None	None	N
K/N	0.8402	likely_pathogenic	0.854	pathogenic	0.111	Stabilizing	0.999	D	0.806	deleterious	N	0.466374673	None	None	N
K/P	0.8557	likely_pathogenic	0.8794	pathogenic	0.267	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
K/Q	0.3227	likely_benign	0.3403	ambiguous	-0.027	Destabilizing	0.996	D	0.809	deleterious	N	0.516398502	None	None	N
K/R	0.0907	likely_benign	0.0952	benign	-0.08	Destabilizing	0.99	D	0.717	prob.delet.	N	0.502853201	None	None	N
K/S	0.8371	likely_pathogenic	0.8505	pathogenic	-0.491	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
K/T	0.3761	ambiguous	0.3943	ambiguous	-0.284	Destabilizing	0.998	D	0.795	deleterious	N	0.443078887	None	None	N
K/V	0.4692	ambiguous	0.4775	ambiguous	0.267	Stabilizing	0.99	D	0.769	deleterious	None	None	None	None	N
K/W	0.9014	likely_pathogenic	0.9131	pathogenic	-0.2	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/Y	0.8592	likely_pathogenic	0.8707	pathogenic	0.148	Stabilizing	0.998	D	0.804	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.