TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17985	54178;54179;54180	chr2:178605224;178605223;178605222	chr2:179469951;179469950;179469949
N2AB	16344	49255;49256;49257	chr2:178605224;178605223;178605222	chr2:179469951;179469950;179469949
N2A	15417	46474;46475;46476	chr2:178605224;178605223;178605222	chr2:179469951;179469950;179469949
N2B	8920	26983;26984;26985	chr2:178605224;178605223;178605222	chr2:179469951;179469950;179469949
Novex-1	9045	27358;27359;27360	chr2:178605224;178605223;178605222	chr2:179469951;179469950;179469949
Novex-2	9112	27559;27560;27561	chr2:178605224;178605223;178605222	chr2:179469951;179469950;179469949
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-114
• Domain position: 18
• Structural Position: 29
• Q(SASA): 0.6237
• 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
H/Q	rs374042312	None	0.006	N	0.235	0.032	0.124217242631	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
H/Q	rs374042312	None	0.006	N	0.235	0.032	0.124217242631	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/Q	rs374042312	None	0.006	N	0.235	0.032	0.124217242631	gnomAD-4.0.0	3.85367E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.1948E-06	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
H/A	0.1366	likely_benign	0.1425	benign	-0.052	Destabilizing	0.002	N	0.34	neutral	None	None	None	None	N
H/C	0.1158	likely_benign	0.1124	benign	0.565	Stabilizing	0.245	N	0.455	neutral	None	None	None	None	N
H/D	0.1499	likely_benign	0.1437	benign	-0.337	Destabilizing	0.001	N	0.251	neutral	N	0.405491652	None	None	N
H/E	0.1881	likely_benign	0.1813	benign	-0.265	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
H/F	0.2026	likely_benign	0.1973	benign	1.022	Stabilizing	0.085	N	0.487	neutral	None	None	None	None	N
H/G	0.2378	likely_benign	0.2273	benign	-0.401	Destabilizing	0.002	N	0.33	neutral	None	None	None	None	N
H/I	0.1313	likely_benign	0.1372	benign	0.886	Stabilizing	0.018	N	0.482	neutral	None	None	None	None	N
H/K	0.124	likely_benign	0.1265	benign	-0.109	Destabilizing	0.002	N	0.317	neutral	None	None	None	None	N
H/L	0.0971	likely_benign	0.0912	benign	0.886	Stabilizing	0.006	N	0.359	neutral	N	0.404912862	None	None	N
H/M	0.227	likely_benign	0.2385	benign	0.61	Stabilizing	0.497	N	0.491	neutral	None	None	None	None	N
H/N	0.0552	likely_benign	0.0551	benign	-0.188	Destabilizing	None	N	0.153	neutral	N	0.411436189	None	None	N
H/P	0.4743	ambiguous	0.4227	ambiguous	0.598	Stabilizing	0.014	N	0.397	neutral	N	0.480277412	None	None	N
H/Q	0.0996	likely_benign	0.0996	benign	0.027	Stabilizing	0.006	N	0.235	neutral	N	0.400296476	None	None	N
H/R	0.0803	likely_benign	0.0751	benign	-0.839	Destabilizing	0.006	N	0.225	neutral	N	0.379054412	None	None	N
H/S	0.1072	likely_benign	0.1111	benign	-0.042	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
H/T	0.1025	likely_benign	0.1053	benign	0.136	Stabilizing	0.002	N	0.368	neutral	None	None	None	None	N
H/V	0.1091	likely_benign	0.1147	benign	0.598	Stabilizing	0.018	N	0.369	neutral	None	None	None	None	N
H/W	0.3862	ambiguous	0.3634	ambiguous	1.153	Stabilizing	0.497	N	0.459	neutral	None	None	None	None	N
H/Y	0.0959	likely_benign	0.0916	benign	1.304	Stabilizing	0.028	N	0.393	neutral	N	0.446087481	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.