TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15622	47089;47090;47091	chr2:178618686;178618685;178618684	chr2:179483413;179483412;179483411
N2AB	13981	42166;42167;42168	chr2:178618686;178618685;178618684	chr2:179483413;179483412;179483411
N2A	13054	39385;39386;39387	chr2:178618686;178618685;178618684	chr2:179483413;179483412;179483411
N2B	6557	19894;19895;19896	chr2:178618686;178618685;178618684	chr2:179483413;179483412;179483411
Novex-1	6682	20269;20270;20271	chr2:178618686;178618685;178618684	chr2:179483413;179483412;179483411
Novex-2	6749	20470;20471;20472	chr2:178618686;178618685;178618684	chr2:179483413;179483412;179483411
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-108
• Domain position: 55
• Structural Position: 138
• Q(SASA): 0.0841
• 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	rs758851565	-0.227	0.91	N	0.695	0.254	0.296329037015	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/L	rs758851565	-0.227	0.91	N	0.695	0.254	0.296329037015	gnomAD-4.0.0	1.59483E-06	None	None	None	None	N	None	0	0	None	0	2.78489E-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
F/A	0.9158	likely_pathogenic	0.9158	pathogenic	-1.793	Destabilizing	0.985	D	0.772	deleterious	None	None	None	None	N
F/C	0.4879	ambiguous	0.5335	ambiguous	-1.21	Destabilizing	1.0	D	0.812	deleterious	N	0.449679269	None	None	N
F/D	0.9949	likely_pathogenic	0.994	pathogenic	-2.718	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
F/E	0.9891	likely_pathogenic	0.9865	pathogenic	-2.469	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
F/G	0.9684	likely_pathogenic	0.9686	pathogenic	-2.265	Highly Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
F/H	0.8457	likely_pathogenic	0.847	pathogenic	-1.473	Destabilizing	0.991	D	0.747	deleterious	None	None	None	None	N
F/I	0.4629	ambiguous	0.5127	ambiguous	-0.264	Destabilizing	0.98	D	0.706	prob.neutral	N	0.445502572	None	None	N
F/K	0.9767	likely_pathogenic	0.974	pathogenic	-1.576	Destabilizing	0.996	D	0.858	deleterious	None	None	None	None	N
F/L	0.8367	likely_pathogenic	0.8612	pathogenic	-0.264	Destabilizing	0.91	D	0.695	prob.neutral	N	0.375286567	None	None	N
F/M	0.7026	likely_pathogenic	0.7257	pathogenic	-0.243	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
F/N	0.974	likely_pathogenic	0.9669	pathogenic	-2.261	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
F/P	0.9992	likely_pathogenic	0.9991	pathogenic	-0.785	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
F/Q	0.9599	likely_pathogenic	0.9553	pathogenic	-1.993	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
F/R	0.9433	likely_pathogenic	0.9388	pathogenic	-1.635	Destabilizing	0.996	D	0.864	deleterious	None	None	None	None	N
F/S	0.932	likely_pathogenic	0.9353	pathogenic	-2.737	Highly Destabilizing	0.994	D	0.818	deleterious	N	0.45037515	None	None	N
F/T	0.9516	likely_pathogenic	0.9526	pathogenic	-2.353	Highly Destabilizing	0.996	D	0.814	deleterious	None	None	None	None	N
F/V	0.4744	ambiguous	0.5177	ambiguous	-0.785	Destabilizing	0.961	D	0.729	prob.delet.	N	0.444311126	None	None	N
F/W	0.6179	likely_pathogenic	0.6494	pathogenic	0.153	Stabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
F/Y	0.1873	likely_benign	0.1955	benign	-0.143	Destabilizing	0.122	N	0.233	neutral	N	0.448991685	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.