TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18118	54577;54578;54579	chr2:178604737;178604736;178604735	chr2:179469464;179469463;179469462
N2AB	16477	49654;49655;49656	chr2:178604737;178604736;178604735	chr2:179469464;179469463;179469462
N2A	15550	46873;46874;46875	chr2:178604737;178604736;178604735	chr2:179469464;179469463;179469462
N2B	9053	27382;27383;27384	chr2:178604737;178604736;178604735	chr2:179469464;179469463;179469462
Novex-1	9178	27757;27758;27759	chr2:178604737;178604736;178604735	chr2:179469464;179469463;179469462
Novex-2	9245	27958;27959;27960	chr2:178604737;178604736;178604735	chr2:179469464;179469463;179469462
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: Fn3-19
• Domain position: 54
• Structural Position: 69
• Q(SASA): 0.1323
• 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	0.76	N	0.528	0.168	0.21737058555	gnomAD-4.0.0	1.59636E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42248E-04	0	0	0
T/I	rs373881551	None	0.991	N	0.757	0.42	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1385	likely_benign	0.167	benign	-1.09	Destabilizing	0.76	D	0.528	neutral	N	0.458723996	None	None	N
T/C	0.4438	ambiguous	0.5104	ambiguous	-0.679	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
T/D	0.6466	likely_pathogenic	0.6971	pathogenic	-0.474	Destabilizing	0.986	D	0.709	prob.delet.	None	None	None	None	N
T/E	0.6877	likely_pathogenic	0.7631	pathogenic	-0.412	Destabilizing	0.986	D	0.711	prob.delet.	None	None	None	None	N
T/F	0.6278	likely_pathogenic	0.7579	pathogenic	-1.077	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
T/G	0.3296	likely_benign	0.3948	ambiguous	-1.405	Destabilizing	0.91	D	0.627	neutral	None	None	None	None	N
T/H	0.5696	likely_pathogenic	0.6651	pathogenic	-1.625	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
T/I	0.5042	ambiguous	0.6784	pathogenic	-0.321	Destabilizing	0.991	D	0.757	deleterious	N	0.509920821	None	None	N
T/K	0.6216	likely_pathogenic	0.7371	pathogenic	-0.737	Destabilizing	0.986	D	0.715	prob.delet.	None	None	None	None	N
T/L	0.2632	likely_benign	0.3551	ambiguous	-0.321	Destabilizing	0.953	D	0.627	neutral	None	None	None	None	N
T/M	0.1913	likely_benign	0.2314	benign	-0.068	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
T/N	0.2162	likely_benign	0.2784	benign	-0.921	Destabilizing	0.982	D	0.685	prob.neutral	N	0.463569668	None	None	N
T/P	0.7454	likely_pathogenic	0.8309	pathogenic	-0.545	Destabilizing	0.991	D	0.763	deleterious	N	0.470727356	None	None	N
T/Q	0.5195	ambiguous	0.6266	pathogenic	-0.967	Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
T/R	0.5631	ambiguous	0.68	pathogenic	-0.609	Destabilizing	0.986	D	0.769	deleterious	None	None	None	None	N
T/S	0.1319	likely_benign	0.1444	benign	-1.225	Destabilizing	0.17	N	0.305	neutral	N	0.426128788	None	None	N
T/V	0.3446	ambiguous	0.4762	ambiguous	-0.545	Destabilizing	0.953	D	0.594	neutral	None	None	None	None	N
T/W	0.8676	likely_pathogenic	0.9129	pathogenic	-1.028	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
T/Y	0.6546	likely_pathogenic	0.7657	pathogenic	-0.768	Destabilizing	0.998	D	0.758	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.