TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7225	21898;21899;21900	chr2:178723427;178723426;178723425	chr2:179588154;179588153;179588152
N2AB	6908	20947;20948;20949	chr2:178723427;178723426;178723425	chr2:179588154;179588153;179588152
N2A	5981	18166;18167;18168	chr2:178723427;178723426;178723425	chr2:179588154;179588153;179588152
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-56
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.4713
• 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
F/L	None	None	0.454	N	0.343	0.197	0.366085729538	gnomAD-4.0.0	1.59947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87256E-06	0	0
F/S	rs780534846	-1.853	0.051	N	0.318	0.219	0.570720304676	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.66E-05	None	0	8.95E-06	0
F/S	rs780534846	-1.853	0.051	N	0.318	0.219	0.570720304676	gnomAD-4.0.0	2.74246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80157E-06	2.3316E-05	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
F/A	0.256	likely_benign	0.28	benign	-1.51	Destabilizing	0.525	D	0.398	neutral	None	None	None	None	N
F/C	0.3267	likely_benign	0.3312	benign	-0.706	Destabilizing	0.997	D	0.429	neutral	N	0.499695661	None	None	N
F/D	0.441	ambiguous	0.4731	ambiguous	0.447	Stabilizing	0.949	D	0.443	neutral	None	None	None	None	N
F/E	0.5527	ambiguous	0.5458	ambiguous	0.476	Stabilizing	0.949	D	0.451	neutral	None	None	None	None	N
F/G	0.5851	likely_pathogenic	0.6206	pathogenic	-1.77	Destabilizing	0.728	D	0.459	neutral	None	None	None	None	N
F/H	0.2934	likely_benign	0.2837	benign	-0.007	Destabilizing	0.949	D	0.407	neutral	None	None	None	None	N
F/I	0.1445	likely_benign	0.1472	benign	-0.787	Destabilizing	0.801	D	0.389	neutral	N	0.444072336	None	None	N
F/K	0.6084	likely_pathogenic	0.589	pathogenic	-0.572	Destabilizing	0.949	D	0.448	neutral	None	None	None	None	N
F/L	0.6244	likely_pathogenic	0.6185	pathogenic	-0.787	Destabilizing	0.454	N	0.343	neutral	N	0.445053771	None	None	N
F/M	0.3961	ambiguous	0.3923	ambiguous	-0.637	Destabilizing	0.991	D	0.397	neutral	None	None	None	None	N
F/N	0.3137	likely_benign	0.3484	ambiguous	-0.57	Destabilizing	0.949	D	0.451	neutral	None	None	None	None	N
F/P	0.9542	likely_pathogenic	0.9597	pathogenic	-1.013	Destabilizing	0.974	D	0.487	neutral	None	None	None	None	N
F/Q	0.4977	ambiguous	0.478	ambiguous	-0.622	Destabilizing	0.974	D	0.483	neutral	None	None	None	None	N
F/R	0.4412	ambiguous	0.4261	ambiguous	0.022	Stabilizing	0.949	D	0.485	neutral	None	None	None	None	N
F/S	0.1434	likely_benign	0.1641	benign	-1.38	Destabilizing	0.051	N	0.318	neutral	N	0.452363745	None	None	N
F/T	0.1858	likely_benign	0.2061	benign	-1.26	Destabilizing	0.029	N	0.223	neutral	None	None	None	None	N
F/V	0.1511	likely_benign	0.1478	benign	-1.013	Destabilizing	0.669	D	0.389	neutral	N	0.464447608	None	None	N
F/W	0.3968	ambiguous	0.3843	ambiguous	-0.119	Destabilizing	0.993	D	0.401	neutral	None	None	None	None	N
F/Y	0.1222	likely_benign	0.1185	benign	-0.274	Destabilizing	0.012	N	0.277	neutral	N	0.465141041	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.