TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21884	65875;65876;65877	chr2:178583153;178583152;178583151	chr2:179447880;179447879;179447878
N2AB	20243	60952;60953;60954	chr2:178583153;178583152;178583151	chr2:179447880;179447879;179447878
N2A	19316	58171;58172;58173	chr2:178583153;178583152;178583151	chr2:179447880;179447879;179447878
N2B	12819	38680;38681;38682	chr2:178583153;178583152;178583151	chr2:179447880;179447879;179447878
Novex-1	12944	39055;39056;39057	chr2:178583153;178583152;178583151	chr2:179447880;179447879;179447878
Novex-2	13011	39256;39257;39258	chr2:178583153;178583152;178583151	chr2:179447880;179447879;179447878
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-125
• Domain position: 19
• Structural Position: 31
• Q(SASA): 0.2539
• 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/N	rs1350675904	-0.839	0.549	N	0.489	0.214	0.30212335484	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
D/N	rs1350675904	-0.839	0.549	N	0.489	0.214	0.30212335484	gnomAD-4.0.0	4.78348E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.59161E-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
D/A	0.2191	likely_benign	0.1816	benign	-0.301	Destabilizing	0.016	N	0.416	neutral	N	0.488497903	None	None	N
D/C	0.7764	likely_pathogenic	0.6869	pathogenic	0.016	Stabilizing	0.992	D	0.615	neutral	None	None	None	None	N
D/E	0.1446	likely_benign	0.1268	benign	-0.484	Destabilizing	0.002	N	0.221	neutral	N	0.398683976	None	None	N
D/F	0.7368	likely_pathogenic	0.6694	pathogenic	0.013	Stabilizing	0.972	D	0.603	neutral	None	None	None	None	N
D/G	0.2639	likely_benign	0.2223	benign	-0.596	Destabilizing	0.549	D	0.472	neutral	D	0.534155622	None	None	N
D/H	0.3218	likely_benign	0.2572	benign	-0.088	Destabilizing	0.896	D	0.546	neutral	N	0.481900005	None	None	N
D/I	0.4969	ambiguous	0.4189	ambiguous	0.451	Stabilizing	0.85	D	0.595	neutral	None	None	None	None	N
D/K	0.4095	ambiguous	0.3263	benign	0.139	Stabilizing	0.447	N	0.467	neutral	None	None	None	None	N
D/L	0.4618	ambiguous	0.3865	ambiguous	0.451	Stabilizing	0.617	D	0.544	neutral	None	None	None	None	N
D/M	0.6626	likely_pathogenic	0.5904	pathogenic	0.706	Stabilizing	0.992	D	0.605	neutral	None	None	None	None	N
D/N	0.1193	likely_benign	0.1115	benign	-0.323	Destabilizing	0.549	D	0.489	neutral	N	0.478915628	None	None	N
D/P	0.7078	likely_pathogenic	0.6933	pathogenic	0.225	Stabilizing	0.005	N	0.352	neutral	None	None	None	None	N
D/Q	0.3236	likely_benign	0.2647	benign	-0.215	Destabilizing	0.447	N	0.495	neutral	None	None	None	None	N
D/R	0.4808	ambiguous	0.3903	ambiguous	0.314	Stabilizing	0.85	D	0.601	neutral	None	None	None	None	N
D/S	0.1517	likely_benign	0.1328	benign	-0.467	Destabilizing	0.25	N	0.463	neutral	None	None	None	None	N
D/T	0.2639	likely_benign	0.2238	benign	-0.225	Destabilizing	0.021	N	0.391	neutral	None	None	None	None	N
D/V	0.2754	likely_benign	0.2286	benign	0.225	Stabilizing	0.549	D	0.51	neutral	N	0.481900005	None	None	N
D/W	0.9324	likely_pathogenic	0.9051	pathogenic	0.193	Stabilizing	0.992	D	0.647	neutral	None	None	None	None	N
D/Y	0.3497	ambiguous	0.2921	benign	0.27	Stabilizing	0.963	D	0.603	neutral	N	0.51574322	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.