TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15362	46309;46310;46311	chr2:178620437;178620436;178620435	chr2:179485164;179485163;179485162
N2AB	13721	41386;41387;41388	chr2:178620437;178620436;178620435	chr2:179485164;179485163;179485162
N2A	12794	38605;38606;38607	chr2:178620437;178620436;178620435	chr2:179485164;179485163;179485162
N2B	6297	19114;19115;19116	chr2:178620437;178620436;178620435	chr2:179485164;179485163;179485162
Novex-1	6422	19489;19490;19491	chr2:178620437;178620436;178620435	chr2:179485164;179485163;179485162
Novex-2	6489	19690;19691;19692	chr2:178620437;178620436;178620435	chr2:179485164;179485163;179485162
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-105
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.3323
• 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
D/E	rs2058092096	None	0.17	N	0.316	0.06	0.0920862733494	gnomAD-4.0.0	1.59442E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86443E-06	0	0
D/G	rs779619831	-0.39	0.885	N	0.535	0.292	0.144782658237	gnomAD-4.0.0	1.59441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43451E-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
D/A	0.4144	ambiguous	0.4784	ambiguous	-0.369	Destabilizing	0.939	D	0.559	neutral	D	0.522869181	None	None	N
D/C	0.8988	likely_pathogenic	0.9234	pathogenic	0.075	Stabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
D/E	0.3039	likely_benign	0.3866	ambiguous	-0.389	Destabilizing	0.17	N	0.316	neutral	N	0.453478943	None	None	N
D/F	0.8071	likely_pathogenic	0.8453	pathogenic	-0.441	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
D/G	0.3075	likely_benign	0.3767	ambiguous	-0.588	Destabilizing	0.885	D	0.535	neutral	N	0.444820515	None	None	N
D/H	0.5899	likely_pathogenic	0.6599	pathogenic	-0.578	Destabilizing	0.998	D	0.676	prob.neutral	N	0.442025166	None	None	N
D/I	0.7575	likely_pathogenic	0.804	pathogenic	0.164	Stabilizing	0.993	D	0.761	deleterious	None	None	None	None	N
D/K	0.6877	likely_pathogenic	0.7473	pathogenic	0.075	Stabilizing	0.953	D	0.581	neutral	None	None	None	None	N
D/L	0.7272	likely_pathogenic	0.779	pathogenic	0.164	Stabilizing	0.993	D	0.751	deleterious	None	None	None	None	N
D/M	0.8799	likely_pathogenic	0.9147	pathogenic	0.497	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
D/N	0.1433	likely_benign	0.1788	benign	-0.113	Destabilizing	0.1	N	0.302	neutral	N	0.440154992	None	None	N
D/P	0.9554	likely_pathogenic	0.9642	pathogenic	0.009	Stabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
D/Q	0.6383	likely_pathogenic	0.7102	pathogenic	-0.082	Destabilizing	0.986	D	0.658	neutral	None	None	None	None	N
D/R	0.7067	likely_pathogenic	0.7596	pathogenic	0.131	Stabilizing	0.986	D	0.721	prob.delet.	None	None	None	None	N
D/S	0.279	likely_benign	0.3401	ambiguous	-0.263	Destabilizing	0.91	D	0.495	neutral	None	None	None	None	N
D/T	0.5693	likely_pathogenic	0.6322	pathogenic	-0.099	Destabilizing	0.986	D	0.594	neutral	None	None	None	None	N
D/V	0.5482	ambiguous	0.595	pathogenic	0.009	Stabilizing	0.991	D	0.753	deleterious	D	0.568360247	None	None	N
D/W	0.959	likely_pathogenic	0.9689	pathogenic	-0.359	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
D/Y	0.3479	ambiguous	0.3712	ambiguous	-0.231	Destabilizing	0.999	D	0.753	deleterious	D	0.568192344	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.