TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1018	3277;3278;3279	chr2:178782854;178782853;178782852	chr2:179647581;179647580;179647579
N2AB	1018	3277;3278;3279	chr2:178782854;178782853;178782852	chr2:179647581;179647580;179647579
N2A	1018	3277;3278;3279	chr2:178782854;178782853;178782852	chr2:179647581;179647580;179647579
N2B	972	3139;3140;3141	chr2:178782854;178782853;178782852	chr2:179647581;179647580;179647579
Novex-1	972	3139;3140;3141	chr2:178782854;178782853;178782852	chr2:179647581;179647580;179647579
Novex-2	972	3139;3140;3141	chr2:178782854;178782853;178782852	chr2:179647581;179647580;179647579
Novex-3	1018	3277;3278;3279	chr2:178782854;178782853;178782852	chr2:179647581;179647580;179647579

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-3
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.3066
• 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
V/A	rs878967057	None	0.001	N	0.089	0.149	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs878967057	None	0.001	N	0.089	0.149	None	gnomAD-4.0.0	6.56927E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46977E-05	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
V/A	0.1937	likely_benign	0.2179	benign	-1.204	Destabilizing	0.001	N	0.089	neutral	N	0.497897518	None	None	I
V/C	0.8244	likely_pathogenic	0.8491	pathogenic	-0.927	Destabilizing	0.836	D	0.481	neutral	None	None	None	None	I
V/D	0.4689	ambiguous	0.5378	ambiguous	-1.284	Destabilizing	0.418	N	0.546	neutral	None	None	None	None	I
V/E	0.2267	likely_benign	0.2496	benign	-1.364	Destabilizing	0.183	N	0.465	neutral	N	0.449857546	None	None	I
V/F	0.2088	likely_benign	0.2297	benign	-1.32	Destabilizing	0.716	D	0.483	neutral	None	None	None	None	I
V/G	0.2892	likely_benign	0.3371	benign	-1.414	Destabilizing	0.101	N	0.5	neutral	N	0.510966168	None	None	I
V/H	0.5371	ambiguous	0.5786	pathogenic	-0.928	Destabilizing	0.94	D	0.543	neutral	None	None	None	None	I
V/I	0.0822	likely_benign	0.0812	benign	-0.763	Destabilizing	0.101	N	0.326	neutral	N	0.495240634	None	None	I
V/K	0.2143	likely_benign	0.2171	benign	-0.89	Destabilizing	0.228	N	0.463	neutral	None	None	None	None	I
V/L	0.2016	likely_benign	0.2278	benign	-0.763	Destabilizing	0.017	N	0.208	neutral	N	0.50557758	None	None	I
V/M	0.1054	likely_benign	0.1089	benign	-0.495	Destabilizing	0.01	N	0.215	neutral	None	None	None	None	I
V/N	0.3098	likely_benign	0.3399	benign	-0.662	Destabilizing	0.418	N	0.553	neutral	None	None	None	None	I
V/P	0.972	likely_pathogenic	0.9828	pathogenic	-0.876	Destabilizing	0.593	D	0.536	neutral	None	None	None	None	I
V/Q	0.228	likely_benign	0.2446	benign	-0.987	Destabilizing	0.593	D	0.535	neutral	None	None	None	None	I
V/R	0.2172	likely_benign	0.2368	benign	-0.283	Destabilizing	0.418	N	0.578	neutral	None	None	None	None	I
V/S	0.2083	likely_benign	0.23	benign	-1.082	Destabilizing	0.004	N	0.213	neutral	None	None	None	None	I
V/T	0.1432	likely_benign	0.1479	benign	-1.068	Destabilizing	0.001	N	0.112	neutral	None	None	None	None	I
V/W	0.8426	likely_pathogenic	0.88	pathogenic	-1.393	Destabilizing	0.983	D	0.533	neutral	None	None	None	None	I
V/Y	0.6377	likely_pathogenic	0.6668	pathogenic	-1.091	Destabilizing	0.836	D	0.479	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.