TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29779	89560;89561;89562	chr2:178553670;178553669;178553668	chr2:179418397;179418396;179418395
N2AB	28138	84637;84638;84639	chr2:178553670;178553669;178553668	chr2:179418397;179418396;179418395
N2A	27211	81856;81857;81858	chr2:178553670;178553669;178553668	chr2:179418397;179418396;179418395
N2B	20714	62365;62366;62367	chr2:178553670;178553669;178553668	chr2:179418397;179418396;179418395
Novex-1	20839	62740;62741;62742	chr2:178553670;178553669;178553668	chr2:179418397;179418396;179418395
Novex-2	20906	62941;62942;62943	chr2:178553670;178553669;178553668	chr2:179418397;179418396;179418395
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: Fn3-105
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0326
• 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	None	None	0.001	N	0.227	0.073	0.222439326576	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05

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	0.0949	likely_benign	0.0904	benign	0.022	Stabilizing	0.024	N	0.48	neutral	N	0.497087596	None	None	N
E/C	0.6502	likely_pathogenic	0.6469	pathogenic	-0.236	Destabilizing	0.864	D	0.422	neutral	None	None	None	None	N
E/D	0.0855	likely_benign	0.0844	benign	-0.244	Destabilizing	None	N	0.207	neutral	N	0.458281279	None	None	N
E/F	0.5452	ambiguous	0.5405	ambiguous	-0.073	Destabilizing	0.628	D	0.433	neutral	None	None	None	None	N
E/G	0.0809	likely_benign	0.0793	benign	-0.077	Destabilizing	0.055	N	0.425	neutral	N	0.435689634	None	None	N
E/H	0.3192	likely_benign	0.3109	benign	0.575	Stabilizing	0.356	N	0.455	neutral	None	None	None	None	N
E/I	0.2109	likely_benign	0.1998	benign	0.222	Stabilizing	0.214	N	0.445	neutral	None	None	None	None	N
E/K	0.091	likely_benign	0.0851	benign	0.351	Stabilizing	0.001	N	0.227	neutral	N	0.467919482	None	None	N
E/L	0.2133	likely_benign	0.2027	benign	0.222	Stabilizing	0.072	N	0.431	neutral	None	None	None	None	N
E/M	0.2573	likely_benign	0.2403	benign	-0.056	Destabilizing	0.356	N	0.447	neutral	None	None	None	None	N
E/N	0.1316	likely_benign	0.1256	benign	0.231	Stabilizing	0.038	N	0.415	neutral	None	None	None	None	N
E/P	0.2528	likely_benign	0.2584	benign	0.172	Stabilizing	0.136	N	0.487	neutral	None	None	None	None	N
E/Q	0.1186	likely_benign	0.114	benign	0.217	Stabilizing	0.001	N	0.204	neutral	N	0.473594661	None	None	N
E/R	0.173	likely_benign	0.1681	benign	0.596	Stabilizing	None	N	0.316	neutral	None	None	None	None	N
E/S	0.1159	likely_benign	0.1137	benign	0.046	Stabilizing	0.016	N	0.404	neutral	None	None	None	None	N
E/T	0.1071	likely_benign	0.1054	benign	0.131	Stabilizing	0.001	N	0.361	neutral	None	None	None	None	N
E/V	0.1348	likely_benign	0.1256	benign	0.172	Stabilizing	0.055	N	0.446	neutral	N	0.484601089	None	None	N
E/W	0.7294	likely_pathogenic	0.7172	pathogenic	-0.051	Destabilizing	0.864	D	0.427	neutral	None	None	None	None	N
E/Y	0.4193	ambiguous	0.4126	ambiguous	0.146	Stabilizing	0.628	D	0.443	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.