TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22483	67672;67673;67674	chr2:178579750;178579749;178579748	chr2:179444477;179444476;179444475
N2AB	20842	62749;62750;62751	chr2:178579750;178579749;178579748	chr2:179444477;179444476;179444475
N2A	19915	59968;59969;59970	chr2:178579750;178579749;178579748	chr2:179444477;179444476;179444475
N2B	13418	40477;40478;40479	chr2:178579750;178579749;178579748	chr2:179444477;179444476;179444475
Novex-1	13543	40852;40853;40854	chr2:178579750;178579749;178579748	chr2:179444477;179444476;179444475
Novex-2	13610	41053;41054;41055	chr2:178579750;178579749;178579748	chr2:179444477;179444476;179444475
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-51
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1716
• 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
I/V	rs1291879446	-1.522	0.198	N	0.251	0.125	0.471211772063	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs1291879446	-1.522	0.198	N	0.251	0.125	0.471211772063	gnomAD-4.0.0	1.59227E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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
I/A	0.9662	likely_pathogenic	0.9555	pathogenic	-2.519	Highly Destabilizing	0.983	D	0.663	neutral	None	None	None	None	I
I/C	0.9625	likely_pathogenic	0.9457	pathogenic	-1.591	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
I/D	0.991	likely_pathogenic	0.9903	pathogenic	-2.513	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	I
I/E	0.9817	likely_pathogenic	0.98	pathogenic	-2.351	Highly Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	I
I/F	0.8747	likely_pathogenic	0.842	pathogenic	-1.57	Destabilizing	0.997	D	0.732	prob.delet.	D	0.525359743	None	None	I
I/G	0.9882	likely_pathogenic	0.9844	pathogenic	-3.01	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
I/H	0.9838	likely_pathogenic	0.9792	pathogenic	-2.325	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
I/K	0.9672	likely_pathogenic	0.9607	pathogenic	-1.937	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
I/L	0.3408	ambiguous	0.2902	benign	-1.128	Destabilizing	0.798	D	0.465	neutral	N	0.475642108	None	None	I
I/M	0.4488	ambiguous	0.3818	ambiguous	-0.868	Destabilizing	0.997	D	0.689	prob.neutral	D	0.527894639	None	None	I
I/N	0.7324	likely_pathogenic	0.7435	pathogenic	-2.048	Highly Destabilizing	0.999	D	0.803	deleterious	D	0.540264902	None	None	I
I/P	0.9501	likely_pathogenic	0.937	pathogenic	-1.569	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
I/Q	0.9739	likely_pathogenic	0.9682	pathogenic	-2.03	Highly Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	I
I/R	0.9588	likely_pathogenic	0.9527	pathogenic	-1.464	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	I
I/S	0.9482	likely_pathogenic	0.9403	pathogenic	-2.745	Highly Destabilizing	0.997	D	0.76	deleterious	D	0.528148128	None	None	I
I/T	0.9441	likely_pathogenic	0.927	pathogenic	-2.451	Highly Destabilizing	0.978	D	0.759	deleterious	N	0.507575111	None	None	I
I/V	0.1747	likely_benign	0.138	benign	-1.569	Destabilizing	0.198	N	0.251	neutral	N	0.492356567	None	None	I
I/W	0.994	likely_pathogenic	0.991	pathogenic	-1.885	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
I/Y	0.9655	likely_pathogenic	0.9569	pathogenic	-1.638	Destabilizing	0.999	D	0.729	prob.delet.	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.