TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1308	4147;4148;4149	chr2:178779270;178779269;178779268	chr2:179643997;179643996;179643995
N2AB	1308	4147;4148;4149	chr2:178779270;178779269;178779268	chr2:179643997;179643996;179643995
N2A	1308	4147;4148;4149	chr2:178779270;178779269;178779268	chr2:179643997;179643996;179643995
N2B	1262	4009;4010;4011	chr2:178779270;178779269;178779268	chr2:179643997;179643996;179643995
Novex-1	1262	4009;4010;4011	chr2:178779270;178779269;178779268	chr2:179643997;179643996;179643995
Novex-2	1262	4009;4010;4011	chr2:178779270;178779269;178779268	chr2:179643997;179643996;179643995
Novex-3	1308	4147;4148;4149	chr2:178779270;178779269;178779268	chr2:179643997;179643996;179643995

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-5
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1161
• 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
V/A	None	None	0.003	N	0.295	0.182	0.341226946553	gnomAD-4.0.0	1.20043E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31262E-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
V/A	0.4235	ambiguous	0.4744	ambiguous	-1.786	Destabilizing	0.003	N	0.295	neutral	N	0.451655138	None	None	N
V/C	0.9186	likely_pathogenic	0.9301	pathogenic	-1.42	Destabilizing	0.973	D	0.723	prob.delet.	None	None	None	None	N
V/D	0.9887	likely_pathogenic	0.9925	pathogenic	-1.885	Destabilizing	0.782	D	0.829	deleterious	D	0.647348978	None	None	N
V/E	0.9698	likely_pathogenic	0.9792	pathogenic	-1.656	Destabilizing	0.826	D	0.783	deleterious	None	None	None	None	N
V/F	0.778	likely_pathogenic	0.847	pathogenic	-1.043	Destabilizing	0.879	D	0.763	deleterious	N	0.497356276	None	None	N
V/G	0.7555	likely_pathogenic	0.8019	pathogenic	-2.315	Highly Destabilizing	0.338	N	0.755	deleterious	D	0.575482657	None	None	N
V/H	0.9933	likely_pathogenic	0.996	pathogenic	-1.9	Destabilizing	0.991	D	0.802	deleterious	None	None	None	None	N
V/I	0.1265	likely_benign	0.144	benign	-0.315	Destabilizing	0.505	D	0.569	neutral	N	0.457141114	None	None	N
V/K	0.9774	likely_pathogenic	0.9837	pathogenic	-1.432	Destabilizing	0.826	D	0.784	deleterious	None	None	None	None	N
V/L	0.6167	likely_pathogenic	0.7031	pathogenic	-0.315	Destabilizing	0.174	N	0.597	neutral	N	0.448106012	None	None	N
V/M	0.5414	ambiguous	0.6466	pathogenic	-0.458	Destabilizing	0.906	D	0.651	neutral	None	None	None	None	N
V/N	0.9645	likely_pathogenic	0.9768	pathogenic	-1.765	Destabilizing	0.826	D	0.827	deleterious	None	None	None	None	N
V/P	0.9903	likely_pathogenic	0.9922	pathogenic	-0.777	Destabilizing	0.906	D	0.799	deleterious	None	None	None	None	N
V/Q	0.9661	likely_pathogenic	0.9768	pathogenic	-1.555	Destabilizing	0.906	D	0.771	deleterious	None	None	None	None	N
V/R	0.964	likely_pathogenic	0.9712	pathogenic	-1.393	Destabilizing	0.826	D	0.825	deleterious	None	None	None	None	N
V/S	0.8342	likely_pathogenic	0.8719	pathogenic	-2.444	Highly Destabilizing	0.404	N	0.739	prob.delet.	None	None	None	None	N
V/T	0.6704	likely_pathogenic	0.7253	pathogenic	-2.045	Highly Destabilizing	0.018	N	0.374	neutral	None	None	None	None	N
V/W	0.9971	likely_pathogenic	0.9983	pathogenic	-1.414	Destabilizing	0.991	D	0.785	deleterious	None	None	None	None	N
V/Y	0.9807	likely_pathogenic	0.9882	pathogenic	-1.022	Destabilizing	0.967	D	0.747	deleterious	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.