TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9776	29551;29552;29553	chr2:178706548;178706547;178706546	chr2:179571275;179571274;179571273
N2AB	9459	28600;28601;28602	chr2:178706548;178706547;178706546	chr2:179571275;179571274;179571273
N2A	8532	25819;25820;25821	chr2:178706548;178706547;178706546	chr2:179571275;179571274;179571273
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-83
• Domain position: 79
• Structural Position: 162
• Q(SASA): 0.7469
• 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
E/D	None	None	0.001	None	0.271	0.092	0.18995819373	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs143477225	0.7	None	None	0.113	0.123	None	gnomAD-2.1.1	3.61E-05	None	None	None	None	I	None	6.46E-05	2.9E-05	None	0	0	None	6.54E-05	None	0	4.43E-05	0
E/K	rs143477225	0.7	None	None	0.113	0.123	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	rs143477225	0.7	None	None	0.113	0.123	None	gnomAD-4.0.0	2.16879E-05	None	None	None	None	I	None	1.33294E-05	3.33344E-05	None	0	0	None	0	0	2.20379E-05	5.49076E-05	1.60046E-05
E/Q	None	None	None	None	0.129	0.172	0.18995819373	gnomAD-4.0.0	6.84195E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99462E-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
E/A	0.2043	likely_benign	0.1679	benign	-0.191	Destabilizing	None	N	0.187	neutral	None	None	None	None	I
E/C	0.8983	likely_pathogenic	0.878	pathogenic	-0.089	Destabilizing	0.316	N	0.255	neutral	None	None	None	None	I
E/D	0.3013	likely_benign	0.2519	benign	-0.16	Destabilizing	0.001	N	0.271	neutral	None	None	None	None	I
E/F	0.8826	likely_pathogenic	0.8463	pathogenic	-0.197	Destabilizing	0.051	N	0.345	neutral	None	None	None	None	I
E/G	0.2965	likely_benign	0.2258	benign	-0.343	Destabilizing	0.001	N	0.248	neutral	None	None	None	None	I
E/H	0.4538	ambiguous	0.4057	ambiguous	0.258	Stabilizing	0.021	N	0.333	neutral	None	None	None	None	I
E/I	0.4184	ambiguous	0.389	ambiguous	0.16	Stabilizing	0.018	N	0.347	neutral	None	None	None	None	I
E/K	0.045	likely_benign	0.0456	benign	0.314	Stabilizing	None	N	0.113	neutral	None	None	None	None	I
E/L	0.4721	ambiguous	0.4083	ambiguous	0.16	Stabilizing	0.002	N	0.265	neutral	None	None	None	None	I
E/M	0.4276	ambiguous	0.3655	ambiguous	0.072	Stabilizing	0.041	N	0.408	neutral	None	None	None	None	I
E/N	0.3295	likely_benign	0.272	benign	0.182	Stabilizing	0.002	N	0.259	neutral	None	None	None	None	I
E/P	0.4954	ambiguous	0.4232	ambiguous	0.062	Stabilizing	0.008	N	0.348	neutral	None	None	None	None	I
E/Q	0.1007	likely_benign	0.0886	benign	0.194	Stabilizing	None	N	0.129	neutral	None	None	None	None	I
E/R	0.1164	likely_benign	0.1102	benign	0.563	Stabilizing	None	N	0.122	neutral	None	None	None	None	I
E/S	0.2776	likely_benign	0.2227	benign	-0.024	Destabilizing	None	N	0.179	neutral	None	None	None	None	I
E/T	0.2349	likely_benign	0.1933	benign	0.098	Stabilizing	0.002	N	0.313	neutral	None	None	None	None	I
E/V	0.3429	ambiguous	0.296	benign	0.062	Stabilizing	0.001	N	0.346	neutral	None	None	None	None	I
E/W	0.93	likely_pathogenic	0.8953	pathogenic	-0.115	Destabilizing	0.316	N	0.251	neutral	None	None	None	None	I
E/Y	0.7653	likely_pathogenic	0.7167	pathogenic	0.033	Stabilizing	0.018	N	0.312	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.