TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31489	94690;94691;94692	chr2:178547060;178547059;178547058	chr2:179411787;179411786;179411785
N2AB	29848	89767;89768;89769	chr2:178547060;178547059;178547058	chr2:179411787;179411786;179411785
N2A	28921	86986;86987;86988	chr2:178547060;178547059;178547058	chr2:179411787;179411786;179411785
N2B	22424	67495;67496;67497	chr2:178547060;178547059;178547058	chr2:179411787;179411786;179411785
Novex-1	22549	67870;67871;67872	chr2:178547060;178547059;178547058	chr2:179411787;179411786;179411785
Novex-2	22616	68071;68072;68073	chr2:178547060;178547059;178547058	chr2:179411787;179411786;179411785
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-117
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.4489
• 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
A/S	rs773485371	-0.46	0.957	N	0.443	0.304	0.237489013734	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	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
A/C	0.7942	likely_pathogenic	0.7672	pathogenic	-0.908	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
A/D	0.9943	likely_pathogenic	0.9931	pathogenic	-0.654	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	I
A/E	0.9837	likely_pathogenic	0.9807	pathogenic	-0.81	Destabilizing	0.999	D	0.717	prob.delet.	N	0.493663322	None	None	I
A/F	0.9259	likely_pathogenic	0.9237	pathogenic	-0.938	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
A/G	0.6065	likely_pathogenic	0.5435	ambiguous	-0.327	Destabilizing	0.996	D	0.57	neutral	N	0.491434823	None	None	I
A/H	0.9833	likely_pathogenic	0.9778	pathogenic	-0.222	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
A/I	0.7463	likely_pathogenic	0.7879	pathogenic	-0.459	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
A/K	0.9932	likely_pathogenic	0.9916	pathogenic	-0.664	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
A/L	0.8309	likely_pathogenic	0.8338	pathogenic	-0.459	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	I
A/M	0.8347	likely_pathogenic	0.8432	pathogenic	-0.567	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
A/N	0.9721	likely_pathogenic	0.9668	pathogenic	-0.406	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
A/P	0.9881	likely_pathogenic	0.9859	pathogenic	-0.381	Destabilizing	1.0	D	0.767	deleterious	D	0.530685207	None	None	I
A/Q	0.9649	likely_pathogenic	0.956	pathogenic	-0.7	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
A/R	0.9743	likely_pathogenic	0.9685	pathogenic	-0.141	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
A/S	0.2861	likely_benign	0.2606	benign	-0.584	Destabilizing	0.957	D	0.443	neutral	N	0.482929354	None	None	I
A/T	0.6451	likely_pathogenic	0.6555	pathogenic	-0.667	Destabilizing	0.996	D	0.697	prob.neutral	N	0.503173203	None	None	I
A/V	0.3793	ambiguous	0.4384	ambiguous	-0.381	Destabilizing	0.998	D	0.745	deleterious	N	0.508552597	None	None	I
A/W	0.9931	likely_pathogenic	0.9927	pathogenic	-1.028	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
A/Y	0.9738	likely_pathogenic	0.97	pathogenic	-0.717	Destabilizing	1.0	D	0.85	deleterious	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.