TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7821	23686;23687;23688	chr2:178720181;178720180;178720179	chr2:179584908;179584907;179584906
N2AB	7504	22735;22736;22737	chr2:178720181;178720180;178720179	chr2:179584908;179584907;179584906
N2A	6577	19954;19955;19956	chr2:178720181;178720180;178720179	chr2:179584908;179584907;179584906
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-63
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.975
• 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
F/L	rs1478276063	-0.14	0.047	N	0.249	0.288	0.368183359018	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
F/L	rs1478276063	-0.14	0.047	N	0.249	0.288	0.368183359018	gnomAD-4.0.0	8.21097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.07941E-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
F/A	0.2622	likely_benign	0.1828	benign	-0.556	Destabilizing	0.061	N	0.391	neutral	None	None	None	None	I
F/C	0.2281	likely_benign	0.1784	benign	-0.189	Destabilizing	0.794	D	0.511	neutral	N	0.51479907	None	None	I
F/D	0.4315	ambiguous	0.3364	benign	0.683	Stabilizing	0.418	N	0.551	neutral	None	None	None	None	I
F/E	0.569	likely_pathogenic	0.4845	ambiguous	0.638	Stabilizing	0.418	N	0.541	neutral	None	None	None	None	I
F/G	0.5252	ambiguous	0.4129	ambiguous	-0.686	Destabilizing	0.129	N	0.532	neutral	None	None	None	None	I
F/H	0.4093	ambiguous	0.3544	ambiguous	0.4	Stabilizing	0.94	D	0.481	neutral	None	None	None	None	I
F/I	0.1431	likely_benign	0.0996	benign	-0.259	Destabilizing	0.037	N	0.387	neutral	N	0.456982918	None	None	I
F/K	0.7185	likely_pathogenic	0.6346	pathogenic	0.108	Stabilizing	0.418	N	0.547	neutral	None	None	None	None	I
F/L	0.6237	likely_pathogenic	0.5045	ambiguous	-0.259	Destabilizing	0.047	N	0.249	neutral	N	0.450979665	None	None	I
F/M	0.365	ambiguous	0.2819	benign	-0.33	Destabilizing	0.716	D	0.401	neutral	None	None	None	None	I
F/N	0.2789	likely_benign	0.2104	benign	0.129	Stabilizing	0.418	N	0.574	neutral	None	None	None	None	I
F/P	0.7816	likely_pathogenic	0.649	pathogenic	-0.339	Destabilizing	0.593	D	0.533	neutral	None	None	None	None	I
F/Q	0.5407	ambiguous	0.4517	ambiguous	0.097	Stabilizing	0.836	D	0.523	neutral	None	None	None	None	I
F/R	0.6207	likely_pathogenic	0.5357	ambiguous	0.417	Stabilizing	0.418	N	0.532	neutral	None	None	None	None	I
F/S	0.1265	likely_benign	0.0975	benign	-0.41	Destabilizing	0.001	N	0.281	neutral	N	0.358992224	None	None	I
F/T	0.1991	likely_benign	0.1503	benign	-0.367	Destabilizing	0.129	N	0.507	neutral	None	None	None	None	I
F/V	0.1391	likely_benign	0.0978	benign	-0.339	Destabilizing	0.001	N	0.235	neutral	N	0.431353755	None	None	I
F/W	0.5033	ambiguous	0.4504	ambiguous	-0.353	Destabilizing	0.983	D	0.449	neutral	None	None	None	None	I
F/Y	0.1277	likely_benign	0.1155	benign	-0.259	Destabilizing	0.523	D	0.451	neutral	N	0.458599071	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.