TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18008	54247;54248;54249	chr2:178605155;178605154;178605153	chr2:179469882;179469881;179469880
N2AB	16367	49324;49325;49326	chr2:178605155;178605154;178605153	chr2:179469882;179469881;179469880
N2A	15440	46543;46544;46545	chr2:178605155;178605154;178605153	chr2:179469882;179469881;179469880
N2B	8943	27052;27053;27054	chr2:178605155;178605154;178605153	chr2:179469882;179469881;179469880
Novex-1	9068	27427;27428;27429	chr2:178605155;178605154;178605153	chr2:179469882;179469881;179469880
Novex-2	9135	27628;27629;27630	chr2:178605155;178605154;178605153	chr2:179469882;179469881;179469880
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-114
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.6004
• 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/G	None	None	0.22	N	0.539	0.122	0.227934060464	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
E/K	rs2054482853	None	0.22	N	0.525	0.191	0.203808441222	gnomAD-4.0.0	3.18777E-06	None	None	None	None	N	None	0	0	None	9.54563E-05	0	None	0	0	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	0.0994	likely_benign	0.1147	benign	-0.07	Destabilizing	0.22	N	0.549	neutral	N	0.495302793	None	None	N
E/C	0.6875	likely_pathogenic	0.7459	pathogenic	-0.392	Destabilizing	0.968	D	0.674	neutral	None	None	None	None	N
E/D	0.0702	likely_benign	0.0843	benign	-0.396	Destabilizing	None	N	0.203	neutral	N	0.448685069	None	None	N
E/F	0.6189	likely_pathogenic	0.7125	pathogenic	-0.095	Destabilizing	0.89	D	0.617	neutral	None	None	None	None	N
E/G	0.089	likely_benign	0.1029	benign	-0.181	Destabilizing	0.22	N	0.539	neutral	N	0.482354925	None	None	N
E/H	0.3068	likely_benign	0.3663	ambiguous	0.596	Stabilizing	0.726	D	0.466	neutral	None	None	None	None	N
E/I	0.2541	likely_benign	0.3209	benign	0.169	Stabilizing	0.726	D	0.611	neutral	None	None	None	None	N
E/K	0.1273	likely_benign	0.146	benign	0.262	Stabilizing	0.22	N	0.525	neutral	N	0.490435691	None	None	N
E/L	0.2393	likely_benign	0.2896	benign	0.169	Stabilizing	0.567	D	0.589	neutral	None	None	None	None	N
E/M	0.3543	ambiguous	0.4182	ambiguous	-0.153	Destabilizing	0.968	D	0.582	neutral	None	None	None	None	N
E/N	0.1304	likely_benign	0.1564	benign	0.001	Stabilizing	0.157	N	0.491	neutral	None	None	None	None	N
E/P	0.2017	likely_benign	0.2322	benign	0.107	Stabilizing	0.726	D	0.497	neutral	None	None	None	None	N
E/Q	0.1156	likely_benign	0.1234	benign	0.008	Stabilizing	0.22	N	0.455	neutral	N	0.48127749	None	None	N
E/R	0.2188	likely_benign	0.2529	benign	0.57	Stabilizing	0.567	D	0.473	neutral	None	None	None	None	N
E/S	0.1055	likely_benign	0.12	benign	-0.136	Destabilizing	0.157	N	0.511	neutral	None	None	None	None	N
E/T	0.1247	likely_benign	0.1452	benign	-0.037	Destabilizing	0.272	N	0.507	neutral	None	None	None	None	N
E/V	0.155	likely_benign	0.188	benign	0.107	Stabilizing	0.667	D	0.508	neutral	N	0.480754628	None	None	N
E/W	0.7863	likely_pathogenic	0.8509	pathogenic	-0.045	Destabilizing	0.968	D	0.688	prob.neutral	None	None	None	None	N
E/Y	0.4722	ambiguous	0.5652	pathogenic	0.123	Stabilizing	0.89	D	0.573	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.