TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2768	8527;8528;8529	chr2:178770490;178770489;178770488	chr2:179635217;179635216;179635215
N2AB	2768	8527;8528;8529	chr2:178770490;178770489;178770488	chr2:179635217;179635216;179635215
N2A	2768	8527;8528;8529	chr2:178770490;178770489;178770488	chr2:179635217;179635216;179635215
N2B	2722	8389;8390;8391	chr2:178770490;178770489;178770488	chr2:179635217;179635216;179635215
Novex-1	2722	8389;8390;8391	chr2:178770490;178770489;178770488	chr2:179635217;179635216;179635215
Novex-2	2722	8389;8390;8391	chr2:178770490;178770489;178770488	chr2:179635217;179635216;179635215
Novex-3	2768	8527;8528;8529	chr2:178770490;178770489;178770488	chr2:179635217;179635216;179635215

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-17
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.675
• 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
N/I	rs747393998	0.193	0.984	D	0.607	0.712	0.902507848322	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
N/I	rs747393998	0.193	0.984	D	0.607	0.712	0.902507848322	gnomAD-4.0.0	1.59051E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85646E-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
N/A	0.3067	likely_benign	0.3982	ambiguous	-0.337	Destabilizing	0.919	D	0.462	neutral	None	None	None	None	N
N/C	0.3702	ambiguous	0.5131	ambiguous	0.524	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
N/D	0.1152	likely_benign	0.1187	benign	-0.438	Destabilizing	0.896	D	0.421	neutral	D	0.535645774	None	None	N
N/E	0.3582	ambiguous	0.3973	ambiguous	-0.452	Destabilizing	0.919	D	0.38	neutral	None	None	None	None	N
N/F	0.6091	likely_pathogenic	0.7258	pathogenic	-0.615	Destabilizing	0.988	D	0.603	neutral	None	None	None	None	N
N/G	0.2976	likely_benign	0.3644	ambiguous	-0.553	Destabilizing	0.919	D	0.379	neutral	None	None	None	None	N
N/H	0.1085	likely_benign	0.1284	benign	-0.674	Destabilizing	0.059	N	0.308	neutral	D	0.541252459	None	None	N
N/I	0.4584	ambiguous	0.6039	pathogenic	0.156	Stabilizing	0.984	D	0.607	neutral	D	0.667520784	None	None	N
N/K	0.2864	likely_benign	0.3111	benign	0.028	Stabilizing	0.103	N	0.315	neutral	D	0.547915958	None	None	N
N/L	0.4224	ambiguous	0.54	ambiguous	0.156	Stabilizing	0.976	D	0.524	neutral	None	None	None	None	N
N/M	0.4454	ambiguous	0.5546	ambiguous	0.785	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
N/P	0.8902	likely_pathogenic	0.9367	pathogenic	0.019	Stabilizing	0.996	D	0.532	neutral	None	None	None	None	N
N/Q	0.3011	likely_benign	0.3464	ambiguous	-0.505	Destabilizing	0.976	D	0.363	neutral	None	None	None	None	N
N/R	0.3505	ambiguous	0.3961	ambiguous	0.126	Stabilizing	0.851	D	0.357	neutral	None	None	None	None	N
N/S	0.128	likely_benign	0.1488	benign	-0.194	Destabilizing	0.896	D	0.417	neutral	D	0.547203503	None	None	N
N/T	0.2182	likely_benign	0.2919	benign	-0.068	Destabilizing	0.946	D	0.369	neutral	D	0.605896078	None	None	N
N/V	0.4484	ambiguous	0.5846	pathogenic	0.019	Stabilizing	0.988	D	0.597	neutral	None	None	None	None	N
N/W	0.8052	likely_pathogenic	0.8639	pathogenic	-0.565	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
N/Y	0.1698	likely_benign	0.2201	benign	-0.301	Destabilizing	0.968	D	0.531	neutral	D	0.667608389	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.