TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7895	23908;23909;23910	chr2:178719809;178719808;178719807	chr2:179584536;179584535;179584534
N2AB	7578	22957;22958;22959	chr2:178719809;178719808;178719807	chr2:179584536;179584535;179584534
N2A	6651	20176;20177;20178	chr2:178719809;178719808;178719807	chr2:179584536;179584535;179584534
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-64
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1271
• 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
P/L	None	None	0.026	N	0.579	0.281	0.39798585902	gnomAD-4.0.0	3.19471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87134E-06	1.43794E-05	0
P/S	None	None	0.811	N	0.697	0.441	0.317084106153	gnomAD-4.0.0	6.85389E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00823E-07	0	0
P/T	None	None	0.211	N	0.492	0.376	0.302793454619	gnomAD-4.0.0	1.02808E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.35123E-05	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
P/A	0.1284	likely_benign	0.1128	benign	-1.601	Destabilizing	0.811	D	0.631	neutral	N	0.516518719	None	None	N
P/C	0.8482	likely_pathogenic	0.8206	pathogenic	-0.948	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
P/D	0.9693	likely_pathogenic	0.9612	pathogenic	-1.779	Destabilizing	0.976	D	0.742	deleterious	None	None	None	None	N
P/E	0.9076	likely_pathogenic	0.8868	pathogenic	-1.751	Destabilizing	0.976	D	0.748	deleterious	None	None	None	None	N
P/F	0.9418	likely_pathogenic	0.925	pathogenic	-1.196	Destabilizing	0.976	D	0.859	deleterious	None	None	None	None	N
P/G	0.6963	likely_pathogenic	0.6501	pathogenic	-1.948	Destabilizing	0.976	D	0.755	deleterious	None	None	None	None	N
P/H	0.9027	likely_pathogenic	0.886	pathogenic	-1.672	Destabilizing	0.999	D	0.776	deleterious	N	0.51553024	None	None	N
P/I	0.715	likely_pathogenic	0.6584	pathogenic	-0.727	Destabilizing	0.952	D	0.793	deleterious	None	None	None	None	N
P/K	0.9533	likely_pathogenic	0.9416	pathogenic	-1.513	Destabilizing	0.976	D	0.757	deleterious	None	None	None	None	N
P/L	0.3274	likely_benign	0.2933	benign	-0.727	Destabilizing	0.026	N	0.579	neutral	N	0.499871611	None	None	N
P/M	0.6542	likely_pathogenic	0.5978	pathogenic	-0.505	Destabilizing	0.976	D	0.788	deleterious	None	None	None	None	N
P/N	0.9277	likely_pathogenic	0.9071	pathogenic	-1.298	Destabilizing	0.976	D	0.767	deleterious	None	None	None	None	N
P/Q	0.821	likely_pathogenic	0.7893	pathogenic	-1.426	Destabilizing	0.988	D	0.737	prob.delet.	None	None	None	None	N
P/R	0.895	likely_pathogenic	0.8801	pathogenic	-1.028	Destabilizing	0.984	D	0.765	deleterious	N	0.515023261	None	None	N
P/S	0.5283	ambiguous	0.4803	ambiguous	-1.741	Destabilizing	0.811	D	0.697	prob.neutral	N	0.490082151	None	None	N
P/T	0.3161	likely_benign	0.2763	benign	-1.609	Destabilizing	0.211	N	0.492	neutral	N	0.49205716	None	None	N
P/V	0.4905	ambiguous	0.4341	ambiguous	-0.985	Destabilizing	0.851	D	0.687	prob.neutral	None	None	None	None	N
P/W	0.9808	likely_pathogenic	0.9762	pathogenic	-1.494	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
P/Y	0.9576	likely_pathogenic	0.945	pathogenic	-1.191	Destabilizing	0.996	D	0.862	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.