TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30927	93004;93005;93006	chr2:178548847;178548846;178548845	chr2:179413574;179413573;179413572
N2AB	29286	88081;88082;88083	chr2:178548847;178548846;178548845	chr2:179413574;179413573;179413572
N2A	28359	85300;85301;85302	chr2:178548847;178548846;178548845	chr2:179413574;179413573;179413572
N2B	21862	65809;65810;65811	chr2:178548847;178548846;178548845	chr2:179413574;179413573;179413572
Novex-1	21987	66184;66185;66186	chr2:178548847;178548846;178548845	chr2:179413574;179413573;179413572
Novex-2	22054	66385;66386;66387	chr2:178548847;178548846;178548845	chr2:179413574;179413573;179413572
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-150
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5
• 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
I/K	rs531432790	-0.978	0.999	N	0.635	0.564	0.836495694078	gnomAD-2.1.1	6.31765E-04	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	4.73825E-03	None	0	7.1E-05	4.96853E-04
I/K	rs531432790	-0.978	0.999	N	0.635	0.564	0.836495694078	gnomAD-3.1.2	1.97166E-04	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	6.00663E-03	0
I/K	rs531432790	-0.978	0.999	N	0.635	0.564	0.836495694078	1000 genomes	7.98722E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	4.1E-03	None
I/K	rs531432790	-0.978	0.999	N	0.635	0.564	0.836495694078	gnomAD-4.0.0	3.22298E-04	None	None	None	None	N	None	1.3328E-05	4.99917E-05	None	0	0	None	0	0	2.88181E-05	5.05039E-03	3.52113E-04
I/L	rs1416836304	None	0.104	N	0.209	0.16	0.188950314367	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/L	rs1416836304	None	0.104	N	0.209	0.16	0.188950314367	gnomAD-4.0.0	6.57091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46977E-05	0	0
I/M	None	None	0.997	N	0.451	0.306	0.202086224978	gnomAD-4.0.0	4.77716E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71615E-06	0	3.02425E-05
I/T	None	None	0.998	N	0.457	0.476	0.674404827817	gnomAD-4.0.0	6.15957E-06	None	None	None	None	N	None	5.9755E-05	0	None	0	0	None	0	0	1.79889E-06	5.79656E-05	0
I/V	rs1416836304	-1.067	0.889	N	0.279	0.176	0.395143324098	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	1.11532E-04	None	0	None	0	0	0
I/V	rs1416836304	-1.067	0.889	N	0.279	0.176	0.395143324098	gnomAD-4.0.0	3.18457E-06	None	None	None	None	N	None	0	0	None	0	5.54877E-05	None	0	0	0	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
I/A	0.3713	ambiguous	0.2776	benign	-0.871	Destabilizing	0.996	D	0.391	neutral	None	None	None	None	N
I/C	0.8691	likely_pathogenic	0.8234	pathogenic	-0.966	Destabilizing	1.0	D	0.521	neutral	None	None	None	None	N
I/D	0.9182	likely_pathogenic	0.8552	pathogenic	-0.41	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
I/E	0.8744	likely_pathogenic	0.785	pathogenic	-0.427	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
I/F	0.286	likely_benign	0.237	benign	-0.704	Destabilizing	0.998	D	0.443	neutral	None	None	None	None	N
I/G	0.8452	likely_pathogenic	0.7566	pathogenic	-1.058	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
I/H	0.8554	likely_pathogenic	0.7861	pathogenic	-0.17	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
I/K	0.7402	likely_pathogenic	0.6309	pathogenic	-0.532	Destabilizing	0.999	D	0.635	neutral	N	0.510334613	None	None	N
I/L	0.1323	likely_benign	0.1184	benign	-0.45	Destabilizing	0.104	N	0.209	neutral	N	0.362029742	None	None	N
I/M	0.1214	likely_benign	0.1064	benign	-0.841	Destabilizing	0.997	D	0.451	neutral	N	0.447515286	None	None	N
I/N	0.7057	likely_pathogenic	0.5889	pathogenic	-0.547	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
I/P	0.7583	likely_pathogenic	0.6489	pathogenic	-0.564	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
I/Q	0.8176	likely_pathogenic	0.7226	pathogenic	-0.629	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
I/R	0.6477	likely_pathogenic	0.5299	ambiguous	-0.111	Destabilizing	0.999	D	0.645	neutral	N	0.510334613	None	None	N
I/S	0.5423	ambiguous	0.4271	ambiguous	-0.991	Destabilizing	1.0	D	0.529	neutral	None	None	None	None	N
I/T	0.1972	likely_benign	0.1451	benign	-0.89	Destabilizing	0.998	D	0.457	neutral	N	0.509294463	None	None	N
I/V	0.1053	likely_benign	0.0902	benign	-0.564	Destabilizing	0.889	D	0.279	neutral	N	0.459519004	None	None	N
I/W	0.8506	likely_pathogenic	0.8179	pathogenic	-0.711	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
I/Y	0.7476	likely_pathogenic	0.6817	pathogenic	-0.498	Destabilizing	1.0	D	0.49	neutral	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.