TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6694	20305;20306;20307	chr2:178727285;178727284;178727283	chr2:179592012;179592011;179592010
N2AB	6377	19354;19355;19356	chr2:178727285;178727284;178727283	chr2:179592012;179592011;179592010
N2A	5450	16573;16574;16575	chr2:178727285;178727284;178727283	chr2:179592012;179592011;179592010
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-51
• Domain position: 28
• Structural Position: 41
• Q(SASA): 0.524
• Predicted PPI site: I

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/F	rs774576049	-0.861	0.299	N	0.46	0.324	0.579300295483	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
S/Y	None	None	0.99	D	0.673	0.511	0.679282971961	gnomAD-4.0.0	4.10716E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39858E-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	0.1656	likely_benign	0.1307	benign	-0.103	Destabilizing	0.325	N	0.455	neutral	N	0.487996961	None	None	I
S/C	0.3192	likely_benign	0.301	benign	-0.312	Destabilizing	0.999	D	0.545	neutral	D	0.536855677	None	None	I
S/D	0.7556	likely_pathogenic	0.6909	pathogenic	0.011	Stabilizing	0.977	D	0.443	neutral	None	None	None	None	I
S/E	0.8121	likely_pathogenic	0.7416	pathogenic	-0.085	Destabilizing	0.983	D	0.453	neutral	None	None	None	None	I
S/F	0.2715	likely_benign	0.1986	benign	-0.762	Destabilizing	0.299	N	0.46	neutral	N	0.521573114	None	None	I
S/G	0.2499	likely_benign	0.2291	benign	-0.185	Destabilizing	0.987	D	0.405	neutral	None	None	None	None	I
S/H	0.5517	ambiguous	0.4756	ambiguous	-0.519	Destabilizing	1.0	D	0.518	neutral	None	None	None	None	I
S/I	0.3188	likely_benign	0.2157	benign	-0.022	Destabilizing	0.993	D	0.619	neutral	None	None	None	None	I
S/K	0.8841	likely_pathogenic	0.818	pathogenic	-0.428	Destabilizing	0.987	D	0.446	neutral	None	None	None	None	I
S/L	0.1589	likely_benign	0.1151	benign	-0.022	Destabilizing	0.975	D	0.598	neutral	None	None	None	None	I
S/M	0.3168	likely_benign	0.2584	benign	-0.086	Destabilizing	1.0	D	0.519	neutral	None	None	None	None	I
S/N	0.323	likely_benign	0.2475	benign	-0.129	Destabilizing	0.832	D	0.481	neutral	None	None	None	None	I
S/P	0.8166	likely_pathogenic	0.7833	pathogenic	-0.022	Destabilizing	0.997	D	0.513	neutral	N	0.507395117	None	None	I
S/Q	0.7379	likely_pathogenic	0.6497	pathogenic	-0.346	Destabilizing	0.999	D	0.447	neutral	None	None	None	None	I
S/R	0.8492	likely_pathogenic	0.7623	pathogenic	-0.163	Destabilizing	0.998	D	0.507	neutral	None	None	None	None	I
S/T	0.097	likely_benign	0.0936	benign	-0.211	Destabilizing	0.01	N	0.201	neutral	N	0.505198152	None	None	I
S/V	0.3318	likely_benign	0.2342	benign	-0.022	Destabilizing	0.967	D	0.635	neutral	None	None	None	None	I
S/W	0.5216	ambiguous	0.4626	ambiguous	-0.861	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
S/Y	0.2628	likely_benign	0.2088	benign	-0.539	Destabilizing	0.99	D	0.673	neutral	D	0.526960291	None	None	I

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.