TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6814	20665;20666;20667	chr2:178725882;178725881;178725880	chr2:179590609;179590608;179590607
N2AB	6497	19714;19715;19716	chr2:178725882;178725881;178725880	chr2:179590609;179590608;179590607
N2A	5570	16933;16934;16935	chr2:178725882;178725881;178725880	chr2:179590609;179590608;179590607
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: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-52
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4899
• 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	rs1371961339	-0.74	0.048	N	0.199	0.175	0.406945738958	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86058E-06	0	0
F/V	rs1371961339	None	0.143	N	0.407	0.14	0.554437859526	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86058E-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
F/A	0.3835	ambiguous	0.3492	ambiguous	-1.981	Destabilizing	0.138	N	0.343	neutral	None	None	None	None	N
F/C	0.2362	likely_benign	0.2494	benign	-1.062	Destabilizing	0.004	N	0.297	neutral	N	0.513086917	None	None	N
F/D	0.4855	ambiguous	0.4543	ambiguous	-0.337	Destabilizing	0.64	D	0.509	neutral	None	None	None	None	N
F/E	0.6667	likely_pathogenic	0.651	pathogenic	-0.239	Destabilizing	0.181	N	0.489	neutral	None	None	None	None	N
F/G	0.4449	ambiguous	0.4489	ambiguous	-2.31	Highly Destabilizing	0.424	N	0.471	neutral	None	None	None	None	N
F/H	0.3237	likely_benign	0.3063	benign	-0.513	Destabilizing	0.002	N	0.225	neutral	None	None	None	None	N
F/I	0.1732	likely_benign	0.1525	benign	-0.999	Destabilizing	0.358	N	0.277	neutral	N	0.5127402	None	None	N
F/K	0.6088	likely_pathogenic	0.6167	pathogenic	-1.097	Destabilizing	0.425	N	0.494	neutral	None	None	None	None	N
F/L	0.6308	likely_pathogenic	0.6367	pathogenic	-0.999	Destabilizing	0.048	N	0.199	neutral	N	0.483375379	None	None	N
F/M	0.3813	ambiguous	0.3809	ambiguous	-0.787	Destabilizing	0.599	D	0.361	neutral	None	None	None	None	N
F/N	0.2705	likely_benign	0.2637	benign	-1.197	Destabilizing	0.64	D	0.547	neutral	None	None	None	None	N
F/P	0.9013	likely_pathogenic	0.8926	pathogenic	-1.319	Destabilizing	0.002	N	0.306	neutral	None	None	None	None	N
F/Q	0.5112	ambiguous	0.507	ambiguous	-1.188	Destabilizing	0.348	N	0.564	neutral	None	None	None	None	N
F/R	0.46	ambiguous	0.4601	ambiguous	-0.541	Destabilizing	0.425	N	0.58	neutral	None	None	None	None	N
F/S	0.2041	likely_benign	0.188	benign	-2.031	Highly Destabilizing	0.022	N	0.252	neutral	N	0.429929602	None	None	N
F/T	0.2946	likely_benign	0.2664	benign	-1.836	Destabilizing	0.269	N	0.469	neutral	None	None	None	None	N
F/V	0.1881	likely_benign	0.1666	benign	-1.319	Destabilizing	0.143	N	0.407	neutral	N	0.512393483	None	None	N
F/W	0.4601	ambiguous	0.4471	ambiguous	-0.188	Destabilizing	0.876	D	0.415	neutral	None	None	None	None	N
F/Y	0.0768	likely_benign	0.0724	benign	-0.437	Destabilizing	None	N	0.117	neutral	N	0.475125961	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.