TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6433	19522;19523;19524	chr2:178728629;178728628;178728627	chr2:179593356;179593355;179593354
N2AB	6116	18571;18572;18573	chr2:178728629;178728628;178728627	chr2:179593356;179593355;179593354
N2A	5189	15790;15791;15792	chr2:178728629;178728628;178728627	chr2:179593356;179593355;179593354
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-48
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3035
• 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
M/T	None	None	0.784	N	0.517	0.493	0.810469866474	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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
M/A	0.5798	likely_pathogenic	0.4932	ambiguous	-2.071	Highly Destabilizing	0.495	N	0.392	neutral	None	None	None	None	N
M/C	0.8605	likely_pathogenic	0.8121	pathogenic	-1.495	Destabilizing	0.981	D	0.603	neutral	None	None	None	None	N
M/D	0.9607	likely_pathogenic	0.9267	pathogenic	-0.486	Destabilizing	0.981	D	0.659	neutral	None	None	None	None	N
M/E	0.7824	likely_pathogenic	0.6774	pathogenic	-0.38	Destabilizing	0.936	D	0.623	neutral	None	None	None	None	N
M/F	0.4365	ambiguous	0.3768	ambiguous	-0.845	Destabilizing	0.704	D	0.457	neutral	None	None	None	None	N
M/G	0.8575	likely_pathogenic	0.7856	pathogenic	-2.471	Highly Destabilizing	0.936	D	0.625	neutral	None	None	None	None	N
M/H	0.7884	likely_pathogenic	0.7096	pathogenic	-1.574	Destabilizing	0.995	D	0.593	neutral	None	None	None	None	N
M/I	0.4032	ambiguous	0.3325	benign	-0.983	Destabilizing	0.139	N	0.328	neutral	N	0.363320608	None	None	N
M/K	0.5137	ambiguous	0.3804	ambiguous	-0.661	Destabilizing	0.784	D	0.533	neutral	D	0.523362625	None	None	N
M/L	0.1573	likely_benign	0.1256	benign	-0.983	Destabilizing	0.001	N	0.115	neutral	N	0.414634863	None	None	N
M/N	0.8027	likely_pathogenic	0.7367	pathogenic	-0.652	Destabilizing	0.981	D	0.649	neutral	None	None	None	None	N
M/P	0.9442	likely_pathogenic	0.9189	pathogenic	-1.321	Destabilizing	0.981	D	0.651	neutral	None	None	None	None	N
M/Q	0.5137	ambiguous	0.4353	ambiguous	-0.571	Destabilizing	0.981	D	0.569	neutral	None	None	None	None	N
M/R	0.5221	ambiguous	0.3925	ambiguous	-0.428	Destabilizing	0.784	D	0.643	neutral	N	0.51976496	None	None	N
M/S	0.6178	likely_pathogenic	0.5441	ambiguous	-1.383	Destabilizing	0.828	D	0.504	neutral	None	None	None	None	N
M/T	0.3014	likely_benign	0.2407	benign	-1.14	Destabilizing	0.784	D	0.517	neutral	N	0.498696254	None	None	N
M/V	0.0942	likely_benign	0.0862	benign	-1.321	Destabilizing	0.139	N	0.291	neutral	N	0.465655542	None	None	N
M/W	0.8234	likely_pathogenic	0.7481	pathogenic	-0.814	Destabilizing	0.995	D	0.589	neutral	None	None	None	None	N
M/Y	0.7613	likely_pathogenic	0.6817	pathogenic	-0.857	Destabilizing	0.981	D	0.645	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.