TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22216	66871;66872;66873	chr2:178581622;178581621;178581620	chr2:179446349;179446348;179446347
N2AB	20575	61948;61949;61950	chr2:178581622;178581621;178581620	chr2:179446349;179446348;179446347
N2A	19648	59167;59168;59169	chr2:178581622;178581621;178581620	chr2:179446349;179446348;179446347
N2B	13151	39676;39677;39678	chr2:178581622;178581621;178581620	chr2:179446349;179446348;179446347
Novex-1	13276	40051;40052;40053	chr2:178581622;178581621;178581620	chr2:179446349;179446348;179446347
Novex-2	13343	40252;40253;40254	chr2:178581622;178581621;178581620	chr2:179446349;179446348;179446347
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-49
• Domain position: 61
• Structural Position: 90
• Q(SASA): 0.4244
• 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
R/C	rs1365775589	-0.645	0.999	N	0.473	0.268	0.60829468558	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	8.91E-06	0
R/C	rs1365775589	-0.645	0.999	N	0.473	0.268	0.60829468558	gnomAD-4.0.0	8.90043E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29913E-06	6.95894E-05	0
R/H	None	-1.062	0.031	N	0.247	0.155	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	1.29349E-04	0	None	0	5.64E-05	None	0	None	0	3.56E-05	0
R/H	None	-1.062	0.031	N	0.247	0.155	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	4.83E-05	1.31182E-04	0	0	0	None	0	0	1.47E-05	0	0
R/H	None	-1.062	0.031	N	0.247	0.155	None	gnomAD-4.0.0	4.46481E-05	None	None	None	None	I	None	9.35329E-05	3.33778E-05	None	0	4.47928E-05	None	0	0	4.91851E-05	0	4.80893E-05
R/L	rs753717922	None	0.653	N	0.414	0.225	0.441017621159	gnomAD-4.0.0	2.7386E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59952E-06	0	0
R/P	rs753717922	-0.088	0.902	N	0.506	0.291	0.364141725642	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/P	rs753717922	-0.088	0.902	N	0.506	0.291	0.364141725642	gnomAD-4.0.0	6.8465E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99881E-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
R/A	0.3896	ambiguous	0.3625	ambiguous	-0.631	Destabilizing	0.495	N	0.373	neutral	None	None	None	None	I
R/C	0.1752	likely_benign	0.1697	benign	-0.81	Destabilizing	0.999	D	0.473	neutral	N	0.473409927	None	None	I
R/D	0.6531	likely_pathogenic	0.6295	pathogenic	-0.054	Destabilizing	0.329	N	0.411	neutral	None	None	None	None	I
R/E	0.3555	ambiguous	0.3344	benign	0.096	Stabilizing	0.176	N	0.28	neutral	None	None	None	None	I
R/F	0.5325	ambiguous	0.5209	ambiguous	-0.454	Destabilizing	0.944	D	0.486	neutral	None	None	None	None	I
R/G	0.388	ambiguous	0.3476	ambiguous	-0.917	Destabilizing	0.485	N	0.397	neutral	N	0.5112089	None	None	I
R/H	0.0883	likely_benign	0.091	benign	-1.171	Destabilizing	0.031	N	0.247	neutral	N	0.444754621	None	None	I
R/I	0.2518	likely_benign	0.2431	benign	0.136	Stabilizing	0.944	D	0.539	neutral	None	None	None	None	I
R/K	0.121	likely_benign	0.1102	benign	-0.43	Destabilizing	0.004	N	0.176	neutral	None	None	None	None	I
R/L	0.2965	likely_benign	0.2919	benign	0.136	Stabilizing	0.653	D	0.414	neutral	N	0.504821645	None	None	I
R/M	0.3054	likely_benign	0.2769	benign	-0.472	Destabilizing	0.981	D	0.484	neutral	None	None	None	None	I
R/N	0.4772	ambiguous	0.4483	ambiguous	-0.393	Destabilizing	0.003	N	0.235	neutral	None	None	None	None	I
R/P	0.9557	likely_pathogenic	0.9495	pathogenic	-0.1	Destabilizing	0.902	D	0.506	neutral	N	0.507880593	None	None	I
R/Q	0.1064	likely_benign	0.0993	benign	-0.385	Destabilizing	0.031	N	0.233	neutral	None	None	None	None	I
R/S	0.3947	ambiguous	0.3642	ambiguous	-1.017	Destabilizing	0.485	N	0.376	neutral	N	0.394899017	None	None	I
R/T	0.1906	likely_benign	0.1722	benign	-0.678	Destabilizing	0.495	N	0.382	neutral	None	None	None	None	I
R/V	0.2959	likely_benign	0.2853	benign	-0.1	Destabilizing	0.828	D	0.492	neutral	None	None	None	None	I
R/W	0.2749	likely_benign	0.268	benign	-0.266	Destabilizing	0.995	D	0.481	neutral	None	None	None	None	I
R/Y	0.3752	ambiguous	0.3742	ambiguous	0.032	Stabilizing	0.704	D	0.561	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.