TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18439	55540;55541;55542	chr2:178601775;178601774;178601773	chr2:179466502;179466501;179466500
N2AB	16798	50617;50618;50619	chr2:178601775;178601774;178601773	chr2:179466502;179466501;179466500
N2A	15871	47836;47837;47838	chr2:178601775;178601774;178601773	chr2:179466502;179466501;179466500
N2B	9374	28345;28346;28347	chr2:178601775;178601774;178601773	chr2:179466502;179466501;179466500
Novex-1	9499	28720;28721;28722	chr2:178601775;178601774;178601773	chr2:179466502;179466501;179466500
Novex-2	9566	28921;28922;28923	chr2:178601775;178601774;178601773	chr2:179466502;179466501;179466500
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-115
• Domain position: 58
• Structural Position: 131
• Q(SASA): 0.7544
• 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
E/D	None	None	0.001	N	0.114	0.037	0.292787519742	gnomAD-4.0.0	1.37737E-06	None	None	None	None	N	None	0	0	None	0	5.06175E-05	None	0	0	0	0	0
E/G	None	None	0.549	N	0.242	0.199	0.394230963961	gnomAD-4.0.0	1.61583E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88424E-06	0	0
E/K	rs866683190	0.799	0.004	N	0.145	0.208	0.342865806769	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.21E-06	0
E/K	rs866683190	0.799	0.004	N	0.145	0.208	0.342865806769	gnomAD-4.0.0	4.14132E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.0556E-03	0	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	0.1145	likely_benign	0.1416	benign	0.033	Stabilizing	0.201	N	0.263	neutral	N	0.493618509	None	None	N
E/C	0.7746	likely_pathogenic	0.8659	pathogenic	0.017	Stabilizing	0.992	D	0.232	neutral	None	None	None	None	N
E/D	0.0941	likely_benign	0.1128	benign	-0.273	Destabilizing	0.001	N	0.114	neutral	N	0.3931663	None	None	N
E/F	0.7065	likely_pathogenic	0.8053	pathogenic	-0.119	Destabilizing	0.972	D	0.205	neutral	None	None	None	None	N
E/G	0.102	likely_benign	0.1508	benign	-0.065	Destabilizing	0.549	D	0.242	neutral	N	0.466893267	None	None	N
E/H	0.4345	ambiguous	0.5539	ambiguous	0.399	Stabilizing	0.92	D	0.219	neutral	None	None	None	None	N
E/I	0.3204	likely_benign	0.4024	ambiguous	0.227	Stabilizing	0.92	D	0.238	neutral	None	None	None	None	N
E/K	0.1173	likely_benign	0.1813	benign	0.512	Stabilizing	0.004	N	0.145	neutral	N	0.488770049	None	None	N
E/L	0.3684	ambiguous	0.456	ambiguous	0.227	Stabilizing	0.617	D	0.272	neutral	None	None	None	None	N
E/M	0.4499	ambiguous	0.5321	ambiguous	0.098	Stabilizing	0.992	D	0.2	neutral	None	None	None	None	N
E/N	0.201	likely_benign	0.2633	benign	0.387	Stabilizing	0.447	N	0.187	neutral	None	None	None	None	N
E/P	0.2594	likely_benign	0.3382	benign	0.18	Stabilizing	0.766	D	0.273	neutral	None	None	None	None	N
E/Q	0.1428	likely_benign	0.1799	benign	0.374	Stabilizing	0.379	N	0.21	neutral	D	0.537332	None	None	N
E/R	0.223	likely_benign	0.3316	benign	0.645	Stabilizing	0.447	N	0.251	neutral	None	None	None	None	N
E/S	0.1509	likely_benign	0.1906	benign	0.239	Stabilizing	0.25	N	0.219	neutral	None	None	None	None	N
E/T	0.1866	likely_benign	0.2483	benign	0.323	Stabilizing	0.617	D	0.257	neutral	None	None	None	None	N
E/V	0.1981	likely_benign	0.2637	benign	0.18	Stabilizing	0.549	D	0.263	neutral	N	0.519517031	None	None	N
E/W	0.84	likely_pathogenic	0.9181	pathogenic	-0.114	Destabilizing	0.992	D	0.345	neutral	None	None	None	None	N
E/Y	0.556	ambiguous	0.6872	pathogenic	0.099	Stabilizing	0.972	D	0.205	neutral	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.