TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29958	90097;90098;90099	chr2:178553028;178553027;178553026	chr2:179417755;179417754;179417753
N2AB	28317	85174;85175;85176	chr2:178553028;178553027;178553026	chr2:179417755;179417754;179417753
N2A	27390	82393;82394;82395	chr2:178553028;178553027;178553026	chr2:179417755;179417754;179417753
N2B	20893	62902;62903;62904	chr2:178553028;178553027;178553026	chr2:179417755;179417754;179417753
Novex-1	21018	63277;63278;63279	chr2:178553028;178553027;178553026	chr2:179417755;179417754;179417753
Novex-2	21085	63478;63479;63480	chr2:178553028;178553027;178553026	chr2:179417755;179417754;179417753
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-106
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.817
• 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
L/F	rs1700014716	None	0.987	N	0.466	0.325	0.535584383668	gnomAD-4.0.0	2.40101E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62542E-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
L/A	0.1726	likely_benign	0.1524	benign	-0.516	Destabilizing	0.983	D	0.496	neutral	None	None	None	None	I
L/C	0.51	ambiguous	0.4977	ambiguous	-0.754	Destabilizing	1.0	D	0.515	neutral	None	None	None	None	I
L/D	0.5551	ambiguous	0.525	ambiguous	-0.432	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
L/E	0.2815	likely_benign	0.2576	benign	-0.526	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
L/F	0.1779	likely_benign	0.1528	benign	-0.623	Destabilizing	0.987	D	0.466	neutral	N	0.512577271	None	None	I
L/G	0.4638	ambiguous	0.4244	ambiguous	-0.636	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
L/H	0.2449	likely_benign	0.2266	benign	0.08	Stabilizing	0.998	D	0.625	neutral	N	0.486839693	None	None	I
L/I	0.0815	likely_benign	0.078	benign	-0.322	Destabilizing	0.956	D	0.471	neutral	N	0.504224212	None	None	I
L/K	0.2475	likely_benign	0.238	benign	-0.405	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	I
L/M	0.1118	likely_benign	0.107	benign	-0.584	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	I
L/N	0.2994	likely_benign	0.2683	benign	-0.265	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	I
L/P	0.3006	likely_benign	0.2774	benign	-0.357	Destabilizing	0.999	D	0.646	neutral	N	0.473290888	None	None	I
L/Q	0.1334	likely_benign	0.1267	benign	-0.48	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	I
L/R	0.2141	likely_benign	0.21	benign	0.138	Stabilizing	0.997	D	0.602	neutral	N	0.4690117	None	None	I
L/S	0.2165	likely_benign	0.1855	benign	-0.627	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	I
L/T	0.1915	likely_benign	0.1708	benign	-0.62	Destabilizing	0.995	D	0.446	neutral	None	None	None	None	I
L/V	0.0801	likely_benign	0.0753	benign	-0.357	Destabilizing	0.37	N	0.233	neutral	N	0.490774912	None	None	I
L/W	0.3334	likely_benign	0.3037	benign	-0.639	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
L/Y	0.3479	ambiguous	0.3195	benign	-0.403	Destabilizing	0.643	D	0.371	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.