TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17549	52870;52871;52872	chr2:178608238;178608237;178608236	chr2:179472965;179472964;179472963
N2AB	15908	47947;47948;47949	chr2:178608238;178608237;178608236	chr2:179472965;179472964;179472963
N2A	14981	45166;45167;45168	chr2:178608238;178608237;178608236	chr2:179472965;179472964;179472963
N2B	8484	25675;25676;25677	chr2:178608238;178608237;178608236	chr2:179472965;179472964;179472963
Novex-1	8609	26050;26051;26052	chr2:178608238;178608237;178608236	chr2:179472965;179472964;179472963
Novex-2	8676	26251;26252;26253	chr2:178608238;178608237;178608236	chr2:179472965;179472964;179472963
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: Fn3-15
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.6184
• 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/E	None	None	0.852	N	0.35	0.257	0.387529464389	gnomAD-4.0.0	6.87402E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.66561E-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
A/C	0.5675	likely_pathogenic	0.5799	pathogenic	-0.804	Destabilizing	0.999	D	0.256	neutral	None	None	None	None	I
A/D	0.3803	ambiguous	0.4339	ambiguous	-0.553	Destabilizing	0.982	D	0.475	neutral	None	None	None	None	I
A/E	0.2503	likely_benign	0.2703	benign	-0.712	Destabilizing	0.852	D	0.35	neutral	N	0.455046186	None	None	I
A/F	0.342	ambiguous	0.3674	ambiguous	-0.922	Destabilizing	0.982	D	0.507	neutral	None	None	None	None	I
A/G	0.2344	likely_benign	0.2437	benign	-0.32	Destabilizing	0.959	D	0.251	neutral	N	0.487961107	None	None	I
A/H	0.4812	ambiguous	0.5046	ambiguous	-0.311	Destabilizing	0.998	D	0.469	neutral	None	None	None	None	I
A/I	0.1592	likely_benign	0.1633	benign	-0.379	Destabilizing	0.17	N	0.291	neutral	None	None	None	None	I
A/K	0.3884	ambiguous	0.4031	ambiguous	-0.619	Destabilizing	0.884	D	0.385	neutral	None	None	None	None	I
A/L	0.1247	likely_benign	0.1309	benign	-0.379	Destabilizing	0.046	N	0.201	neutral	None	None	None	None	I
A/M	0.1682	likely_benign	0.1695	benign	-0.388	Destabilizing	0.982	D	0.36	neutral	None	None	None	None	I
A/N	0.2926	likely_benign	0.3274	benign	-0.332	Destabilizing	0.991	D	0.508	neutral	None	None	None	None	I
A/P	0.5632	ambiguous	0.5985	pathogenic	-0.314	Destabilizing	0.996	D	0.381	neutral	N	0.500415903	None	None	I
A/Q	0.3086	likely_benign	0.3118	benign	-0.633	Destabilizing	0.373	N	0.223	neutral	None	None	None	None	I
A/R	0.3726	ambiguous	0.379	ambiguous	-0.116	Destabilizing	0.982	D	0.369	neutral	None	None	None	None	I
A/S	0.1253	likely_benign	0.1336	benign	-0.523	Destabilizing	0.92	D	0.248	neutral	N	0.430342529	None	None	I
A/T	0.0971	likely_benign	0.0997	benign	-0.604	Destabilizing	0.959	D	0.232	neutral	N	0.496623449	None	None	I
A/V	0.0999	likely_benign	0.0997	benign	-0.314	Destabilizing	0.704	D	0.262	neutral	N	0.460492078	None	None	I
A/W	0.7867	likely_pathogenic	0.7978	pathogenic	-1.04	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	I
A/Y	0.4888	ambiguous	0.5205	ambiguous	-0.699	Destabilizing	0.997	D	0.506	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.