TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1782	5569;5570;5571	chr2:178776520;178776519;178776518	chr2:179641247;179641246;179641245
N2AB	1782	5569;5570;5571	chr2:178776520;178776519;178776518	chr2:179641247;179641246;179641245
N2A	1782	5569;5570;5571	chr2:178776520;178776519;178776518	chr2:179641247;179641246;179641245
N2B	1736	5431;5432;5433	chr2:178776520;178776519;178776518	chr2:179641247;179641246;179641245
Novex-1	1736	5431;5432;5433	chr2:178776520;178776519;178776518	chr2:179641247;179641246;179641245
Novex-2	1736	5431;5432;5433	chr2:178776520;178776519;178776518	chr2:179641247;179641246;179641245
Novex-3	1782	5569;5570;5571	chr2:178776520;178776519;178776518	chr2:179641247;179641246;179641245

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-8
• Domain position: 80
• Structural Position: 162
• Q(SASA): 0.537
• 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
K/R	None	None	0.998	N	0.458	0.323	0.293147016451	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.8384	likely_pathogenic	0.8068	pathogenic	-0.225	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	I
K/C	0.9688	likely_pathogenic	0.957	pathogenic	-0.381	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/D	0.955	likely_pathogenic	0.9511	pathogenic	0.049	Stabilizing	0.998	D	0.469	neutral	None	None	None	None	I
K/E	0.8203	likely_pathogenic	0.7824	pathogenic	0.077	Stabilizing	0.996	D	0.433	neutral	N	0.400312547	None	None	I
K/F	0.9886	likely_pathogenic	0.988	pathogenic	-0.392	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
K/G	0.9292	likely_pathogenic	0.9147	pathogenic	-0.443	Destabilizing	0.997	D	0.446	neutral	None	None	None	None	I
K/H	0.7461	likely_pathogenic	0.7201	pathogenic	-0.696	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	I
K/I	0.8422	likely_pathogenic	0.8182	pathogenic	0.277	Stabilizing	1.0	D	0.643	neutral	N	0.48099163	None	None	I
K/L	0.8596	likely_pathogenic	0.8409	pathogenic	0.277	Stabilizing	1.0	D	0.445	neutral	None	None	None	None	I
K/M	0.8019	likely_pathogenic	0.7659	pathogenic	0.029	Stabilizing	1.0	D	0.569	neutral	None	None	None	None	I
K/N	0.893	likely_pathogenic	0.8881	pathogenic	-0.011	Destabilizing	0.884	D	0.392	neutral	N	0.497234809	None	None	I
K/P	0.8912	likely_pathogenic	0.88	pathogenic	0.137	Stabilizing	1.0	D	0.524	neutral	None	None	None	None	I
K/Q	0.4941	ambiguous	0.4526	ambiguous	-0.13	Destabilizing	0.999	D	0.559	neutral	N	0.496721292	None	None	I
K/R	0.1434	likely_benign	0.1341	benign	-0.162	Destabilizing	0.998	D	0.458	neutral	N	0.463907528	None	None	I
K/S	0.8951	likely_pathogenic	0.8798	pathogenic	-0.517	Destabilizing	0.997	D	0.456	neutral	None	None	None	None	I
K/T	0.6829	likely_pathogenic	0.6423	pathogenic	-0.326	Destabilizing	0.999	D	0.481	neutral	N	0.506645147	None	None	I
K/V	0.8268	likely_pathogenic	0.8011	pathogenic	0.137	Stabilizing	1.0	D	0.535	neutral	None	None	None	None	I
K/W	0.9866	likely_pathogenic	0.9826	pathogenic	-0.395	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
K/Y	0.9566	likely_pathogenic	0.9525	pathogenic	-0.058	Destabilizing	1.0	D	0.593	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.