TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27196	81811;81812;81813	chr2:178564546;178564545;178564544	chr2:179429273;179429272;179429271
N2AB	25555	76888;76889;76890	chr2:178564546;178564545;178564544	chr2:179429273;179429272;179429271
N2A	24628	74107;74108;74109	chr2:178564546;178564545;178564544	chr2:179429273;179429272;179429271
N2B	18131	54616;54617;54618	chr2:178564546;178564545;178564544	chr2:179429273;179429272;179429271
Novex-1	18256	54991;54992;54993	chr2:178564546;178564545;178564544	chr2:179429273;179429272;179429271
Novex-2	18323	55192;55193;55194	chr2:178564546;178564545;178564544	chr2:179429273;179429272;179429271
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-86
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.8324
• 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
Y/S	rs1704959686	None	0.994	N	0.636	0.377	0.435590266561	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	1.30976E-04	0	0	0	None	0	0	0	0	0
Y/S	rs1704959686	None	0.994	N	0.636	0.377	0.435590266561	gnomAD-4.0.0	1.31437E-05	None	None	None	None	I	None	0	1.30976E-04	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
Y/A	0.7572	likely_pathogenic	0.7209	pathogenic	-0.726	Destabilizing	0.968	D	0.513	neutral	None	None	None	None	I
Y/C	0.268	likely_benign	0.2274	benign	0.281	Stabilizing	0.999	D	0.678	prob.neutral	N	0.49864639	None	None	I
Y/D	0.6293	likely_pathogenic	0.5737	pathogenic	0.857	Stabilizing	0.998	D	0.684	prob.neutral	N	0.475125096	None	None	I
Y/E	0.8897	likely_pathogenic	0.8635	pathogenic	0.823	Stabilizing	0.998	D	0.636	neutral	None	None	None	None	I
Y/F	0.1114	likely_benign	0.1224	benign	-0.494	Destabilizing	0.067	N	0.293	neutral	N	0.473762445	None	None	I
Y/G	0.6012	likely_pathogenic	0.5817	pathogenic	-0.912	Destabilizing	0.995	D	0.661	neutral	None	None	None	None	I
Y/H	0.3783	ambiguous	0.3305	benign	0.136	Stabilizing	0.998	D	0.669	neutral	N	0.501410407	None	None	I
Y/I	0.8116	likely_pathogenic	0.7875	pathogenic	-0.266	Destabilizing	0.982	D	0.576	neutral	None	None	None	None	I
Y/K	0.8577	likely_pathogenic	0.8289	pathogenic	0.338	Stabilizing	0.995	D	0.637	neutral	None	None	None	None	I
Y/L	0.7383	likely_pathogenic	0.6891	pathogenic	-0.266	Destabilizing	0.938	D	0.573	neutral	None	None	None	None	I
Y/M	0.8045	likely_pathogenic	0.7848	pathogenic	0.051	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	I
Y/N	0.2552	likely_benign	0.2253	benign	0.259	Stabilizing	0.998	D	0.663	neutral	N	0.479898984	None	None	I
Y/P	0.9876	likely_pathogenic	0.9845	pathogenic	-0.399	Destabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	I
Y/Q	0.806	likely_pathogenic	0.7742	pathogenic	0.219	Stabilizing	0.998	D	0.657	neutral	None	None	None	None	I
Y/R	0.6959	likely_pathogenic	0.6514	pathogenic	0.67	Stabilizing	0.998	D	0.663	neutral	None	None	None	None	I
Y/S	0.3687	ambiguous	0.3179	benign	-0.198	Destabilizing	0.994	D	0.636	neutral	N	0.496599233	None	None	I
Y/T	0.7058	likely_pathogenic	0.665	pathogenic	-0.14	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	I
Y/V	0.6784	likely_pathogenic	0.6481	pathogenic	-0.399	Destabilizing	0.968	D	0.567	neutral	None	None	None	None	I
Y/W	0.4993	ambiguous	0.4765	ambiguous	-0.611	Destabilizing	1.0	D	0.651	neutral	None	None	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.