TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3010	9253;9254;9255	chr2:178768808;178768807;178768806	chr2:179633535;179633534;179633533
N2AB	3010	9253;9254;9255	chr2:178768808;178768807;178768806	chr2:179633535;179633534;179633533
N2A	3010	9253;9254;9255	chr2:178768808;178768807;178768806	chr2:179633535;179633534;179633533
N2B	2964	9115;9116;9117	chr2:178768808;178768807;178768806	chr2:179633535;179633534;179633533
Novex-1	2964	9115;9116;9117	chr2:178768808;178768807;178768806	chr2:179633535;179633534;179633533
Novex-2	2964	9115;9116;9117	chr2:178768808;178768807;178768806	chr2:179633535;179633534;179633533
Novex-3	3010	9253;9254;9255	chr2:178768808;178768807;178768806	chr2:179633535;179633534;179633533

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-20
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.3331
• 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
S/P	None	None	1.0	N	0.687	0.619	0.311387274539	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85647E-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
S/A	0.123	likely_benign	0.1185	benign	-0.228	Destabilizing	0.997	D	0.394	neutral	N	0.491714049	None	None	N
S/C	0.3282	likely_benign	0.3559	ambiguous	-0.145	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
S/D	0.7367	likely_pathogenic	0.7605	pathogenic	0.033	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
S/E	0.8454	likely_pathogenic	0.8517	pathogenic	-0.072	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	N
S/F	0.5585	ambiguous	0.5684	pathogenic	-0.879	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
S/G	0.1609	likely_benign	0.1607	benign	-0.316	Destabilizing	0.999	D	0.479	neutral	None	None	None	None	N
S/H	0.6966	likely_pathogenic	0.7306	pathogenic	-0.792	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
S/I	0.4592	ambiguous	0.4488	ambiguous	-0.128	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
S/K	0.9374	likely_pathogenic	0.9475	pathogenic	-0.423	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	N
S/L	0.231	likely_benign	0.2224	benign	-0.128	Destabilizing	1.0	D	0.607	neutral	N	0.519543168	None	None	N
S/M	0.3411	ambiguous	0.3611	ambiguous	0.096	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
S/N	0.2337	likely_benign	0.2369	benign	-0.075	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
S/P	0.2127	likely_benign	0.2086	benign	-0.134	Destabilizing	1.0	D	0.687	prob.neutral	N	0.424740413	None	None	N
S/Q	0.7914	likely_pathogenic	0.7991	pathogenic	-0.342	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
S/R	0.9187	likely_pathogenic	0.9296	pathogenic	-0.184	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
S/T	0.1699	likely_benign	0.1635	benign	-0.181	Destabilizing	0.999	D	0.447	neutral	N	0.513697889	None	None	N
S/V	0.4434	ambiguous	0.4336	ambiguous	-0.134	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/W	0.6909	likely_pathogenic	0.7151	pathogenic	-0.929	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
S/Y	0.4233	ambiguous	0.4577	ambiguous	-0.632	Destabilizing	1.0	D	0.711	prob.delet.	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.