TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23599	71020;71021;71022	chr2:178575337;178575336;178575335	chr2:179440064;179440063;179440062
N2AB	21958	66097;66098;66099	chr2:178575337;178575336;178575335	chr2:179440064;179440063;179440062
N2A	21031	63316;63317;63318	chr2:178575337;178575336;178575335	chr2:179440064;179440063;179440062
N2B	14534	43825;43826;43827	chr2:178575337;178575336;178575335	chr2:179440064;179440063;179440062
Novex-1	14659	44200;44201;44202	chr2:178575337;178575336;178575335	chr2:179440064;179440063;179440062
Novex-2	14726	44401;44402;44403	chr2:178575337;178575336;178575335	chr2:179440064;179440063;179440062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-59
• Domain position: 68
• Structural Position: 102
• Q(SASA): 0.2481
• 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/K	rs772715686	-0.83	0.003	N	0.239	0.197	0.215109475489	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	8.89E-06	1.65673E-04
E/K	rs772715686	-0.83	0.003	N	0.239	0.197	0.215109475489	gnomAD-4.0.0	6.84326E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.7456E-05	0	6.29687E-06	0	1.65684E-05
E/Q	None	None	0.434	N	0.479	0.109	0.258779203287	gnomAD-4.0.0	6.84326E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99552E-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	0.2455	likely_benign	0.2228	benign	-0.737	Destabilizing	0.003	N	0.21	neutral	N	0.470340925	None	None	N
E/C	0.8775	likely_pathogenic	0.8797	pathogenic	-0.434	Destabilizing	0.984	D	0.473	neutral	None	None	None	None	N
E/D	0.2494	likely_benign	0.2213	benign	-1.169	Destabilizing	0.07	N	0.393	neutral	N	0.520655102	None	None	N
E/F	0.8487	likely_pathogenic	0.8442	pathogenic	0.047	Stabilizing	0.969	D	0.486	neutral	None	None	None	None	N
E/G	0.2749	likely_benign	0.2484	benign	-1.152	Destabilizing	0.491	N	0.319	neutral	N	0.5113049	None	None	N
E/H	0.6265	likely_pathogenic	0.6191	pathogenic	-0.242	Destabilizing	0.879	D	0.358	neutral	None	None	None	None	N
E/I	0.5822	likely_pathogenic	0.5708	pathogenic	0.41	Stabilizing	0.826	D	0.481	neutral	None	None	None	None	N
E/K	0.3138	likely_benign	0.2792	benign	-0.621	Destabilizing	0.003	N	0.239	neutral	N	0.460182647	None	None	N
E/L	0.611	likely_pathogenic	0.5716	pathogenic	0.41	Stabilizing	0.4	N	0.44	neutral	None	None	None	None	N
E/M	0.5245	ambiguous	0.5184	ambiguous	0.834	Stabilizing	0.907	D	0.429	neutral	None	None	None	None	N
E/N	0.4169	ambiguous	0.4006	ambiguous	-1.206	Destabilizing	0.52	D	0.383	neutral	None	None	None	None	N
E/P	0.98	likely_pathogenic	0.9773	pathogenic	0.05	Stabilizing	0.413	N	0.377	neutral	None	None	None	None	N
E/Q	0.1799	likely_benign	0.174	benign	-1.01	Destabilizing	0.434	N	0.479	neutral	N	0.467167334	None	None	N
E/R	0.4804	ambiguous	0.4482	ambiguous	-0.31	Destabilizing	0.416	N	0.401	neutral	None	None	None	None	N
E/S	0.2843	likely_benign	0.2737	benign	-1.55	Destabilizing	0.137	N	0.347	neutral	None	None	None	None	N
E/T	0.3404	ambiguous	0.3269	benign	-1.197	Destabilizing	0.515	D	0.328	neutral	None	None	None	None	N
E/V	0.3571	ambiguous	0.349	ambiguous	0.05	Stabilizing	0.263	N	0.38	neutral	N	0.469148847	None	None	N
E/W	0.9548	likely_pathogenic	0.9536	pathogenic	0.316	Stabilizing	0.997	D	0.563	neutral	None	None	None	None	N
E/Y	0.7705	likely_pathogenic	0.7629	pathogenic	0.313	Stabilizing	0.988	D	0.437	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.