TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26206	78841;78842;78843	chr2:178567516;178567515;178567514	chr2:179432243;179432242;179432241
N2AB	24565	73918;73919;73920	chr2:178567516;178567515;178567514	chr2:179432243;179432242;179432241
N2A	23638	71137;71138;71139	chr2:178567516;178567515;178567514	chr2:179432243;179432242;179432241
N2B	17141	51646;51647;51648	chr2:178567516;178567515;178567514	chr2:179432243;179432242;179432241
Novex-1	17266	52021;52022;52023	chr2:178567516;178567515;178567514	chr2:179432243;179432242;179432241
Novex-2	17333	52222;52223;52224	chr2:178567516;178567515;178567514	chr2:179432243;179432242;179432241
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-137
• Domain position: 14
• Structural Position: 18
• Q(SASA): 0.6064
• 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
N/S	rs1400612460	0.103	0.822	N	0.442	0.23	0.184867976434	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.67673E-04
N/S	rs1400612460	0.103	0.822	N	0.442	0.23	0.184867976434	gnomAD-4.0.0	1.59447E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02957E-05

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
N/A	0.2105	likely_benign	0.241	benign	-0.403	Destabilizing	0.754	D	0.557	neutral	None	None	None	None	I
N/C	0.2079	likely_benign	0.2086	benign	0.247	Stabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
N/D	0.2473	likely_benign	0.307	benign	0.199	Stabilizing	0.822	D	0.451	neutral	N	0.495039874	None	None	I
N/E	0.3886	ambiguous	0.4875	ambiguous	0.19	Stabilizing	0.754	D	0.452	neutral	None	None	None	None	I
N/F	0.4462	ambiguous	0.4426	ambiguous	-0.639	Destabilizing	0.978	D	0.639	neutral	None	None	None	None	I
N/G	0.3065	likely_benign	0.3293	benign	-0.613	Destabilizing	0.86	D	0.441	neutral	None	None	None	None	I
N/H	0.0646	likely_benign	0.0625	benign	-0.547	Destabilizing	0.032	N	0.261	neutral	N	0.483708159	None	None	I
N/I	0.2271	likely_benign	0.2558	benign	0.07	Stabilizing	0.97	D	0.642	neutral	N	0.509662609	None	None	I
N/K	0.185	likely_benign	0.2424	benign	0.06	Stabilizing	0.014	N	0.252	neutral	N	0.415808299	None	None	I
N/L	0.1758	likely_benign	0.195	benign	0.07	Stabilizing	0.956	D	0.58	neutral	None	None	None	None	I
N/M	0.2571	likely_benign	0.2705	benign	0.336	Stabilizing	0.998	D	0.626	neutral	None	None	None	None	I
N/P	0.477	ambiguous	0.4906	ambiguous	-0.059	Destabilizing	0.978	D	0.617	neutral	None	None	None	None	I
N/Q	0.2305	likely_benign	0.261	benign	-0.446	Destabilizing	0.956	D	0.447	neutral	None	None	None	None	I
N/R	0.1976	likely_benign	0.2424	benign	0.087	Stabilizing	0.754	D	0.447	neutral	None	None	None	None	I
N/S	0.0909	likely_benign	0.0962	benign	-0.291	Destabilizing	0.822	D	0.442	neutral	N	0.495845163	None	None	I
N/T	0.1313	likely_benign	0.1561	benign	-0.14	Destabilizing	0.822	D	0.445	neutral	N	0.49667467	None	None	I
N/V	0.2105	likely_benign	0.2363	benign	-0.059	Destabilizing	0.956	D	0.635	neutral	None	None	None	None	I
N/W	0.678	likely_pathogenic	0.6714	pathogenic	-0.572	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	I
N/Y	0.1244	likely_benign	0.1244	benign	-0.32	Destabilizing	0.942	D	0.615	neutral	D	0.53227011	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.