TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5176	15751;15752;15753	chr2:178733863;178733862;178733861	chr2:179598590;179598589;179598588
N2AB	4859	14800;14801;14802	chr2:178733863;178733862;178733861	chr2:179598590;179598589;179598588
N2A	3932	12019;12020;12021	chr2:178733863;178733862;178733861	chr2:179598590;179598589;179598588
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-35
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4994
• 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
D/Y	rs1421517847	0.052	0.975	D	0.404	0.359	0.574670332726	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	2.97E-05	None	0	0	None	0	None	0	0	0
D/Y	rs1421517847	0.052	0.975	D	0.404	0.359	0.574670332726	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.96489E-04	0	0	0	None	0	0	0	0	0
D/Y	rs1421517847	0.052	0.975	D	0.404	0.359	0.574670332726	gnomAD-4.0.0	3.12136E-06	None	None	None	None	N	None	0	6.75721E-05	None	0	0	None	0	0	8.5355E-07	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
D/A	0.2063	likely_benign	0.2774	benign	-0.083	Destabilizing	0.27	N	0.344	neutral	D	0.593891231	None	None	N
D/C	0.6604	likely_pathogenic	0.7743	pathogenic	0.073	Stabilizing	0.995	D	0.386	neutral	None	None	None	None	N
D/E	0.2051	likely_benign	0.2506	benign	-0.172	Destabilizing	0.425	N	0.302	neutral	N	0.513325146	None	None	N
D/F	0.7005	likely_pathogenic	0.8046	pathogenic	-0.037	Destabilizing	0.981	D	0.405	neutral	None	None	None	None	N
D/G	0.1718	likely_benign	0.2262	benign	-0.264	Destabilizing	0.002	N	0.135	neutral	D	0.599221844	None	None	N
D/H	0.2848	likely_benign	0.3642	ambiguous	0.225	Stabilizing	0.927	D	0.389	neutral	D	0.548732623	None	None	N
D/I	0.4719	ambiguous	0.5916	pathogenic	0.34	Stabilizing	0.944	D	0.445	neutral	None	None	None	None	N
D/K	0.4189	ambiguous	0.5234	ambiguous	0.49	Stabilizing	0.704	D	0.296	neutral	None	None	None	None	N
D/L	0.5075	ambiguous	0.6258	pathogenic	0.34	Stabilizing	0.704	D	0.401	neutral	None	None	None	None	N
D/M	0.6938	likely_pathogenic	0.7985	pathogenic	0.334	Stabilizing	0.995	D	0.383	neutral	None	None	None	None	N
D/N	0.0771	likely_benign	0.0927	benign	0.189	Stabilizing	0.002	N	0.071	neutral	N	0.451423017	None	None	N
D/P	0.5736	likely_pathogenic	0.6954	pathogenic	0.221	Stabilizing	0.828	D	0.395	neutral	None	None	None	None	N
D/Q	0.3997	ambiguous	0.5095	ambiguous	0.222	Stabilizing	0.828	D	0.347	neutral	None	None	None	None	N
D/R	0.4465	ambiguous	0.5473	ambiguous	0.655	Stabilizing	0.704	D	0.406	neutral	None	None	None	None	N
D/S	0.1153	likely_benign	0.1391	benign	0.085	Stabilizing	0.013	N	0.075	neutral	None	None	None	None	N
D/T	0.2388	likely_benign	0.3087	benign	0.23	Stabilizing	0.329	N	0.276	neutral	None	None	None	None	N
D/V	0.3185	likely_benign	0.4186	ambiguous	0.221	Stabilizing	0.642	D	0.425	neutral	D	0.561045053	None	None	N
D/W	0.9235	likely_pathogenic	0.9543	pathogenic	0.064	Stabilizing	0.995	D	0.455	neutral	None	None	None	None	N
D/Y	0.2821	likely_benign	0.3733	ambiguous	0.203	Stabilizing	0.975	D	0.404	neutral	D	0.650316935	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.