TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2269	7030;7031;7032	chr2:178774459;178774458;178774457	chr2:179639186;179639185;179639184
N2AB	2269	7030;7031;7032	chr2:178774459;178774458;178774457	chr2:179639186;179639185;179639184
N2A	2269	7030;7031;7032	chr2:178774459;178774458;178774457	chr2:179639186;179639185;179639184
N2B	2223	6892;6893;6894	chr2:178774459;178774458;178774457	chr2:179639186;179639185;179639184
Novex-1	2223	6892;6893;6894	chr2:178774459;178774458;178774457	chr2:179639186;179639185;179639184
Novex-2	2223	6892;6893;6894	chr2:178774459;178774458;178774457	chr2:179639186;179639185;179639184
Novex-3	2269	7030;7031;7032	chr2:178774459;178774458;178774457	chr2:179639186;179639185;179639184

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-12
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.3538
• 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/S	rs1340770955	-2.748	0.986	D	0.593	0.844	0.848023011964	gnomAD-2.1.1	8.01E-06	None	None	None	None	N	None	6.2E-05	2.9E-05	None	0	0	None	0	None	0	0	0
F/S	rs1340770955	-2.748	0.986	D	0.593	0.844	0.848023011964	gnomAD-4.0.0	3.18768E-06	None	None	None	None	N	None	5.65483E-05	2.28802E-05	None	0	0	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	0.8668	likely_pathogenic	0.8575	pathogenic	-2.586	Highly Destabilizing	0.863	D	0.506	neutral	None	None	None	None	N
F/C	0.7542	likely_pathogenic	0.7587	pathogenic	-1.462	Destabilizing	0.999	D	0.644	neutral	D	0.563828782	None	None	N
F/D	0.98	likely_pathogenic	0.9779	pathogenic	-1.796	Destabilizing	0.997	D	0.665	neutral	None	None	None	None	N
F/E	0.9804	likely_pathogenic	0.9787	pathogenic	-1.676	Destabilizing	0.997	D	0.658	neutral	None	None	None	None	N
F/G	0.9665	likely_pathogenic	0.963	pathogenic	-2.969	Highly Destabilizing	0.997	D	0.643	neutral	None	None	None	None	N
F/H	0.9366	likely_pathogenic	0.9284	pathogenic	-1.234	Destabilizing	0.999	D	0.54	neutral	None	None	None	None	N
F/I	0.2743	likely_benign	0.2781	benign	-1.398	Destabilizing	0.134	N	0.229	neutral	N	0.472658216	None	None	N
F/K	0.9824	likely_pathogenic	0.9805	pathogenic	-1.641	Destabilizing	0.997	D	0.65	neutral	None	None	None	None	N
F/L	0.8745	likely_pathogenic	0.8698	pathogenic	-1.398	Destabilizing	0.005	N	0.159	neutral	D	0.524940871	None	None	N
F/M	0.6039	likely_pathogenic	0.5969	pathogenic	-1.03	Destabilizing	0.982	D	0.441	neutral	None	None	None	None	N
F/N	0.9228	likely_pathogenic	0.9154	pathogenic	-1.764	Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
F/P	0.9766	likely_pathogenic	0.9757	pathogenic	-1.793	Destabilizing	0.997	D	0.679	prob.neutral	None	None	None	None	N
F/Q	0.9756	likely_pathogenic	0.973	pathogenic	-1.837	Destabilizing	0.997	D	0.679	prob.neutral	None	None	None	None	N
F/R	0.9684	likely_pathogenic	0.9649	pathogenic	-0.947	Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
F/S	0.8946	likely_pathogenic	0.8839	pathogenic	-2.553	Highly Destabilizing	0.986	D	0.593	neutral	D	0.56325414	None	None	N
F/T	0.8238	likely_pathogenic	0.8104	pathogenic	-2.334	Highly Destabilizing	0.969	D	0.585	neutral	None	None	None	None	N
F/V	0.3777	ambiguous	0.3836	ambiguous	-1.793	Destabilizing	0.704	D	0.437	neutral	N	0.448486524	None	None	N
F/W	0.693	likely_pathogenic	0.6828	pathogenic	-0.49	Destabilizing	0.999	D	0.453	neutral	None	None	None	None	N
F/Y	0.3889	ambiguous	0.3704	ambiguous	-0.771	Destabilizing	0.986	D	0.445	neutral	D	0.56340713	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.