TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15277	46054;46055;46056	chr2:178620781;178620780;178620779	chr2:179485508;179485507;179485506
N2AB	13636	41131;41132;41133	chr2:178620781;178620780;178620779	chr2:179485508;179485507;179485506
N2A	12709	38350;38351;38352	chr2:178620781;178620780;178620779	chr2:179485508;179485507;179485506
N2B	6212	18859;18860;18861	chr2:178620781;178620780;178620779	chr2:179485508;179485507;179485506
Novex-1	6337	19234;19235;19236	chr2:178620781;178620780;178620779	chr2:179485508;179485507;179485506
Novex-2	6404	19435;19436;19437	chr2:178620781;178620780;178620779	chr2:179485508;179485507;179485506
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: Ig-104
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.0914
• Predicted PPI site: N

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	rs1274378566	-1.343	0.976	D	0.858	0.792	0.663428526802	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
Y/C	rs1274378566	-1.343	0.976	D	0.858	0.792	0.663428526802	gnomAD-4.0.0	1.59329E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86266E-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
Y/A	0.9947	likely_pathogenic	0.9931	pathogenic	-2.538	Highly Destabilizing	0.399	N	0.83	deleterious	None	None	None	None	N
Y/C	0.866	likely_pathogenic	0.8494	pathogenic	-2.111	Highly Destabilizing	0.976	D	0.858	deleterious	D	0.725220853	None	None	N
Y/D	0.995	likely_pathogenic	0.9912	pathogenic	-3.496	Highly Destabilizing	0.916	D	0.875	deleterious	D	0.725220853	None	None	N
Y/E	0.998	likely_pathogenic	0.997	pathogenic	-3.261	Highly Destabilizing	0.826	D	0.857	deleterious	None	None	None	None	N
Y/F	0.2185	likely_benign	0.2136	benign	-0.945	Destabilizing	0.001	N	0.367	neutral	D	0.545738876	None	None	N
Y/G	0.9883	likely_pathogenic	0.9837	pathogenic	-2.982	Highly Destabilizing	0.826	D	0.854	deleterious	None	None	None	None	N
Y/H	0.9577	likely_pathogenic	0.9472	pathogenic	-2.244	Highly Destabilizing	0.916	D	0.682	prob.neutral	D	0.725828282	None	None	N
Y/I	0.9128	likely_pathogenic	0.9144	pathogenic	-1.059	Destabilizing	0.539	D	0.769	deleterious	None	None	None	None	N
Y/K	0.9969	likely_pathogenic	0.9956	pathogenic	-2.29	Highly Destabilizing	0.826	D	0.862	deleterious	None	None	None	None	N
Y/L	0.8865	likely_pathogenic	0.8857	pathogenic	-1.059	Destabilizing	0.25	N	0.743	deleterious	None	None	None	None	N
Y/M	0.9777	likely_pathogenic	0.9761	pathogenic	-1.189	Destabilizing	0.947	D	0.779	deleterious	None	None	None	None	N
Y/N	0.9799	likely_pathogenic	0.9731	pathogenic	-3.258	Highly Destabilizing	0.916	D	0.859	deleterious	D	0.725220853	None	None	N
Y/P	0.9982	likely_pathogenic	0.9972	pathogenic	-1.569	Destabilizing	0.935	D	0.885	deleterious	None	None	None	None	N
Y/Q	0.9973	likely_pathogenic	0.9962	pathogenic	-2.845	Highly Destabilizing	0.935	D	0.765	deleterious	None	None	None	None	N
Y/R	0.9901	likely_pathogenic	0.9862	pathogenic	-2.431	Highly Destabilizing	0.826	D	0.857	deleterious	None	None	None	None	N
Y/S	0.9853	likely_pathogenic	0.9809	pathogenic	-3.52	Highly Destabilizing	0.781	D	0.844	deleterious	D	0.725220853	None	None	N
Y/T	0.9922	likely_pathogenic	0.9906	pathogenic	-3.14	Highly Destabilizing	0.826	D	0.849	deleterious	None	None	None	None	N
Y/V	0.8998	likely_pathogenic	0.8913	pathogenic	-1.569	Destabilizing	0.25	N	0.759	deleterious	None	None	None	None	N
Y/W	0.7277	likely_pathogenic	0.7435	pathogenic	-0.381	Destabilizing	0.826	D	0.703	prob.neutral	None	None	None	None	N

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.