TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24349	73270;73271;73272	chr2:178573087;178573086;178573085	chr2:179437814;179437813;179437812
N2AB	22708	68347;68348;68349	chr2:178573087;178573086;178573085	chr2:179437814;179437813;179437812
N2A	21781	65566;65567;65568	chr2:178573087;178573086;178573085	chr2:179437814;179437813;179437812
N2B	15284	46075;46076;46077	chr2:178573087;178573086;178573085	chr2:179437814;179437813;179437812
Novex-1	15409	46450;46451;46452	chr2:178573087;178573086;178573085	chr2:179437814;179437813;179437812
Novex-2	15476	46651;46652;46653	chr2:178573087;178573086;178573085	chr2:179437814;179437813;179437812
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: Fn3-65
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5936
• 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/C	None	None	0.997	N	0.684	0.468	0.404870348458	gnomAD-4.0.0	1.36884E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79928E-06	0	0
Y/N	rs1559421745	None	0.942	N	0.527	0.316	0.412328234245	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/N	rs1559421745	None	0.942	N	0.527	0.316	0.412328234245	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	3.66327E-05

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	0.9234	likely_pathogenic	0.9137	pathogenic	-0.792	Destabilizing	0.754	D	0.567	neutral	None	None	None	None	I
Y/C	0.6067	likely_pathogenic	0.5633	ambiguous	0.075	Stabilizing	0.997	D	0.684	prob.neutral	N	0.487140911	None	None	I
Y/D	0.8781	likely_pathogenic	0.8496	pathogenic	0.977	Stabilizing	0.942	D	0.594	neutral	N	0.471425856	None	None	I
Y/E	0.9714	likely_pathogenic	0.9672	pathogenic	0.96	Stabilizing	0.956	D	0.523	neutral	None	None	None	None	I
Y/F	0.2578	likely_benign	0.2537	benign	-0.405	Destabilizing	0.904	D	0.502	neutral	N	0.512947191	None	None	I
Y/G	0.8782	likely_pathogenic	0.8606	pathogenic	-0.983	Destabilizing	0.754	D	0.559	neutral	None	None	None	None	I
Y/H	0.7355	likely_pathogenic	0.7229	pathogenic	0.153	Stabilizing	0.032	N	0.229	neutral	N	0.511061679	None	None	I
Y/I	0.9171	likely_pathogenic	0.9065	pathogenic	-0.313	Destabilizing	0.978	D	0.567	neutral	None	None	None	None	I
Y/K	0.9582	likely_pathogenic	0.9517	pathogenic	0.179	Stabilizing	0.956	D	0.521	neutral	None	None	None	None	I
Y/L	0.8556	likely_pathogenic	0.828	pathogenic	-0.313	Destabilizing	0.86	D	0.567	neutral	None	None	None	None	I
Y/M	0.9283	likely_pathogenic	0.9081	pathogenic	-0.098	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	I
Y/N	0.7557	likely_pathogenic	0.6942	pathogenic	0.012	Stabilizing	0.942	D	0.527	neutral	N	0.478218542	None	None	I
Y/P	0.9859	likely_pathogenic	0.9887	pathogenic	-0.453	Destabilizing	0.978	D	0.675	prob.neutral	None	None	None	None	I
Y/Q	0.9478	likely_pathogenic	0.94	pathogenic	0.035	Stabilizing	0.956	D	0.571	neutral	None	None	None	None	I
Y/R	0.8793	likely_pathogenic	0.8721	pathogenic	0.478	Stabilizing	0.956	D	0.647	neutral	None	None	None	None	I
Y/S	0.7091	likely_pathogenic	0.6638	pathogenic	-0.47	Destabilizing	0.125	N	0.387	neutral	N	0.472946008	None	None	I
Y/T	0.8944	likely_pathogenic	0.8758	pathogenic	-0.398	Destabilizing	0.915	D	0.525	neutral	None	None	None	None	I
Y/V	0.8547	likely_pathogenic	0.8362	pathogenic	-0.453	Destabilizing	0.956	D	0.515	neutral	None	None	None	None	I
Y/W	0.6625	likely_pathogenic	0.706	pathogenic	-0.481	Destabilizing	0.998	D	0.521	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.