TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15605	47038;47039;47040	chr2:178618737;178618736;178618735	chr2:179483464;179483463;179483462
N2AB	13964	42115;42116;42117	chr2:178618737;178618736;178618735	chr2:179483464;179483463;179483462
N2A	13037	39334;39335;39336	chr2:178618737;178618736;178618735	chr2:179483464;179483463;179483462
N2B	6540	19843;19844;19845	chr2:178618737;178618736;178618735	chr2:179483464;179483463;179483462
Novex-1	6665	20218;20219;20220	chr2:178618737;178618736;178618735	chr2:179483464;179483463;179483462
Novex-2	6732	20419;20420;20421	chr2:178618737;178618736;178618735	chr2:179483464;179483463;179483462
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-108
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.9426
• 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
N/K	rs777985762	0.42	0.669	N	0.279	0.107	0.110078149338	gnomAD-2.1.1	8.1E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	3.27E-05	None	0	0	0
N/K	rs777985762	0.42	0.669	N	0.279	0.107	0.110078149338	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
N/K	rs777985762	0.42	0.669	N	0.279	0.107	0.110078149338	gnomAD-4.0.0	1.8613E-06	None	None	None	None	N	None	1.33736E-05	0	None	0	0	None	0	0	0	1.09864E-05	1.60416E-05
N/S	None	None	0.136	N	0.135	0.067	0.104622674875	gnomAD-4.0.0	3.19062E-06	None	None	None	None	N	None	0	0	None	0	2.79096E-05	None	0	0	0	1.43402E-05	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
N/A	0.1316	likely_benign	0.2254	benign	-0.239	Destabilizing	0.525	D	0.301	neutral	None	None	None	None	N
N/C	0.2891	likely_benign	0.4983	ambiguous	0.278	Stabilizing	0.998	D	0.339	neutral	None	None	None	None	N
N/D	0.0677	likely_benign	0.0959	benign	0.276	Stabilizing	0.005	N	0.105	neutral	N	0.400183728	None	None	N
N/E	0.1422	likely_benign	0.2336	benign	0.258	Stabilizing	0.016	N	0.136	neutral	None	None	None	None	N
N/F	0.4086	ambiguous	0.6136	pathogenic	-0.621	Destabilizing	0.991	D	0.346	neutral	None	None	None	None	N
N/G	0.1434	likely_benign	0.2087	benign	-0.415	Destabilizing	0.007	N	0.102	neutral	None	None	None	None	N
N/H	0.1298	likely_benign	0.1956	benign	-0.405	Destabilizing	0.966	D	0.317	neutral	N	0.454336827	None	None	N
N/I	0.195	likely_benign	0.3278	benign	0.138	Stabilizing	0.966	D	0.375	neutral	N	0.455836331	None	None	N
N/K	0.1581	likely_benign	0.2474	benign	0.112	Stabilizing	0.669	D	0.279	neutral	N	0.449360073	None	None	N
N/L	0.214	likely_benign	0.3526	ambiguous	0.138	Stabilizing	0.842	D	0.426	neutral	None	None	None	None	N
N/M	0.2191	likely_benign	0.3491	ambiguous	0.207	Stabilizing	0.998	D	0.325	neutral	None	None	None	None	N
N/P	0.5252	ambiguous	0.7301	pathogenic	0.04	Stabilizing	0.974	D	0.395	neutral	None	None	None	None	N
N/Q	0.182	likely_benign	0.2894	benign	-0.2	Destabilizing	0.728	D	0.331	neutral	None	None	None	None	N
N/R	0.2257	likely_benign	0.3593	ambiguous	0.117	Stabilizing	0.842	D	0.341	neutral	None	None	None	None	N
N/S	0.0765	likely_benign	0.0993	benign	-0.075	Destabilizing	0.136	N	0.135	neutral	N	0.449158	None	None	N
N/T	0.0923	likely_benign	0.1391	benign	0.052	Stabilizing	0.669	D	0.279	neutral	N	0.45230286	None	None	N
N/V	0.1877	likely_benign	0.3223	benign	0.04	Stabilizing	0.915	D	0.442	neutral	None	None	None	None	N
N/W	0.6076	likely_pathogenic	0.7784	pathogenic	-0.665	Destabilizing	0.998	D	0.451	neutral	None	None	None	None	N
N/Y	0.156	likely_benign	0.2402	benign	-0.37	Destabilizing	0.989	D	0.334	neutral	N	0.455239851	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.