TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16234	48925;48926;48927	chr2:178614907;178614906;178614905	chr2:179479634;179479633;179479632
N2AB	14593	44002;44003;44004	chr2:178614907;178614906;178614905	chr2:179479634;179479633;179479632
N2A	13666	41221;41222;41223	chr2:178614907;178614906;178614905	chr2:179479634;179479633;179479632
N2B	7169	21730;21731;21732	chr2:178614907;178614906;178614905	chr2:179479634;179479633;179479632
Novex-1	7294	22105;22106;22107	chr2:178614907;178614906;178614905	chr2:179479634;179479633;179479632
Novex-2	7361	22306;22307;22308	chr2:178614907;178614906;178614905	chr2:179479634;179479633;179479632
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-5
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.7502
• 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
R/K	None	None	0.122	N	0.262	0.11	0.261217442401	gnomAD-4.0.0	6.96339E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.10845E-07	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
R/A	0.484	ambiguous	0.3743	ambiguous	-0.077	Destabilizing	0.97	D	0.579	neutral	None	None	None	None	I
R/C	0.3232	likely_benign	0.2605	benign	-0.127	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
R/D	0.7695	likely_pathogenic	0.6568	pathogenic	-0.122	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	I
R/E	0.5325	ambiguous	0.4161	ambiguous	-0.072	Destabilizing	0.97	D	0.545	neutral	None	None	None	None	I
R/F	0.6595	likely_pathogenic	0.5858	pathogenic	-0.347	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	I
R/G	0.3519	ambiguous	0.2756	benign	-0.258	Destabilizing	0.98	D	0.544	neutral	N	0.463763828	None	None	I
R/H	0.1791	likely_benign	0.1497	benign	-0.724	Destabilizing	0.999	D	0.491	neutral	None	None	None	None	I
R/I	0.3662	ambiguous	0.2842	benign	0.361	Stabilizing	0.999	D	0.61	neutral	None	None	None	None	I
R/K	0.1135	likely_benign	0.0999	benign	-0.096	Destabilizing	0.122	N	0.262	neutral	N	0.415246149	None	None	I
R/L	0.3479	ambiguous	0.2767	benign	0.361	Stabilizing	0.985	D	0.544	neutral	None	None	None	None	I
R/M	0.4274	ambiguous	0.3398	benign	0.065	Stabilizing	1.0	D	0.529	neutral	N	0.483300358	None	None	I
R/N	0.6813	likely_pathogenic	0.5697	pathogenic	0.214	Stabilizing	0.996	D	0.5	neutral	None	None	None	None	I
R/P	0.6127	likely_pathogenic	0.511	ambiguous	0.235	Stabilizing	0.999	D	0.595	neutral	None	None	None	None	I
R/Q	0.1503	likely_benign	0.1247	benign	0.052	Stabilizing	0.991	D	0.514	neutral	None	None	None	None	I
R/S	0.5625	ambiguous	0.4593	ambiguous	-0.17	Destabilizing	0.961	D	0.589	neutral	N	0.453123974	None	None	I
R/T	0.3723	ambiguous	0.2767	benign	0.005	Stabilizing	0.98	D	0.539	neutral	N	0.477135767	None	None	I
R/V	0.4542	ambiguous	0.3624	ambiguous	0.235	Stabilizing	0.996	D	0.601	neutral	None	None	None	None	I
R/W	0.273	likely_benign	0.2404	benign	-0.385	Destabilizing	1.0	D	0.679	prob.neutral	D	0.548023518	None	None	I
R/Y	0.5156	ambiguous	0.4546	ambiguous	0.023	Stabilizing	0.999	D	0.597	neutral	None	None	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.