TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9678	29257;29258;29259	chr2:178707535;178707534;178707533	chr2:179572262;179572261;179572260
N2AB	9361	28306;28307;28308	chr2:178707535;178707534;178707533	chr2:179572262;179572261;179572260
N2A	8434	25525;25526;25527	chr2:178707535;178707534;178707533	chr2:179572262;179572261;179572260
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-82
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3386
• 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
T/A	None	None	0.001	None	0.204	0.12	0.163833314356	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	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
T/A	0.1	likely_benign	0.1034	benign	-0.823	Destabilizing	0.001	N	0.204	neutral	None	None	None	None	N
T/C	0.5536	ambiguous	0.6054	pathogenic	-0.541	Destabilizing	0.947	D	0.701	prob.neutral	None	None	None	None	N
T/D	0.4296	ambiguous	0.4565	ambiguous	-0.089	Destabilizing	0.7	D	0.692	prob.neutral	None	None	None	None	N
T/E	0.3768	ambiguous	0.3637	ambiguous	-0.084	Destabilizing	0.7	D	0.661	neutral	None	None	None	None	N
T/F	0.2135	likely_benign	0.2305	benign	-0.873	Destabilizing	0.826	D	0.765	deleterious	None	None	None	None	N
T/G	0.3425	ambiguous	0.3845	ambiguous	-1.083	Destabilizing	0.25	N	0.651	neutral	None	None	None	None	N
T/H	0.284	likely_benign	0.2977	benign	-1.347	Destabilizing	0.982	D	0.735	prob.delet.	None	None	None	None	N
T/I	0.1475	likely_benign	0.1444	benign	-0.225	Destabilizing	0.638	D	0.707	prob.neutral	None	None	None	None	N
T/K	0.305	likely_benign	0.2808	benign	-0.664	Destabilizing	0.7	D	0.658	neutral	None	None	None	None	N
T/L	0.114	likely_benign	0.1196	benign	-0.225	Destabilizing	0.25	N	0.58	neutral	None	None	None	None	N
T/M	0.1047	likely_benign	0.1021	benign	0.029	Stabilizing	0.947	D	0.697	prob.neutral	None	None	None	None	N
T/N	0.1335	likely_benign	0.1488	benign	-0.603	Destabilizing	0.781	D	0.643	neutral	None	None	None	None	N
T/P	0.4702	ambiguous	0.5097	ambiguous	-0.392	Destabilizing	0.638	D	0.729	prob.delet.	None	None	None	None	N
T/Q	0.2752	likely_benign	0.2717	benign	-0.774	Destabilizing	0.826	D	0.735	prob.delet.	None	None	None	None	N
T/R	0.2352	likely_benign	0.213	benign	-0.457	Destabilizing	0.7	D	0.734	prob.delet.	None	None	None	None	N
T/S	0.1209	likely_benign	0.1352	benign	-0.926	Destabilizing	0.201	N	0.507	neutral	None	None	None	None	N
T/V	0.1297	likely_benign	0.1357	benign	-0.392	Destabilizing	0.25	N	0.506	neutral	None	None	None	None	N
T/W	0.6276	likely_pathogenic	0.6577	pathogenic	-0.781	Destabilizing	0.982	D	0.759	deleterious	None	None	None	None	N
T/Y	0.3113	likely_benign	0.33	benign	-0.55	Destabilizing	0.826	D	0.766	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.