TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15828	47707;47708;47709	chr2:178617869;178617868;178617867	chr2:179482596;179482595;179482594
N2AB	14187	42784;42785;42786	chr2:178617869;178617868;178617867	chr2:179482596;179482595;179482594
N2A	13260	40003;40004;40005	chr2:178617869;178617868;178617867	chr2:179482596;179482595;179482594
N2B	6763	20512;20513;20514	chr2:178617869;178617868;178617867	chr2:179482596;179482595;179482594
Novex-1	6888	20887;20888;20889	chr2:178617869;178617868;178617867	chr2:179482596;179482595;179482594
Novex-2	6955	21088;21089;21090	chr2:178617869;178617868;178617867	chr2:179482596;179482595;179482594
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: Fn3-2
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.1617
• 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/D	None	None	0.999	N	0.473	0.311	0.251639045875	gnomAD-4.0.0	1.59358E-06	None	None	None	None	N	None	0	0	None	0	2.77948E-05	None	0	0	0	0	0
E/G	None	None	1.0	D	0.705	0.571	0.572690963233	gnomAD-4.0.0	2.73854E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59978E-06	0	0
E/K	rs1246983682	None	0.999	N	0.529	0.369	0.406806705197	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	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	0.284	likely_benign	0.2568	benign	-0.828	Destabilizing	0.999	D	0.623	neutral	N	0.503895116	None	None	N
E/C	0.8985	likely_pathogenic	0.8801	pathogenic	-0.35	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/D	0.2407	likely_benign	0.1946	benign	-1.222	Destabilizing	0.999	D	0.473	neutral	N	0.508627576	None	None	N
E/F	0.823	likely_pathogenic	0.7894	pathogenic	-0.059	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/G	0.406	ambiguous	0.3402	ambiguous	-1.282	Destabilizing	1.0	D	0.705	prob.neutral	D	0.604640679	None	None	N
E/H	0.7697	likely_pathogenic	0.7055	pathogenic	-0.299	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/I	0.4583	ambiguous	0.4349	ambiguous	0.452	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/K	0.5491	ambiguous	0.4534	ambiguous	-0.799	Destabilizing	0.999	D	0.529	neutral	N	0.482665372	None	None	N
E/L	0.5545	ambiguous	0.4812	ambiguous	0.452	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/M	0.5279	ambiguous	0.4884	ambiguous	1.083	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/N	0.4412	ambiguous	0.399	ambiguous	-1.333	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/P	0.7445	likely_pathogenic	0.6965	pathogenic	0.046	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/Q	0.3146	likely_benign	0.274	benign	-1.084	Destabilizing	1.0	D	0.61	neutral	N	0.476139144	None	None	N
E/R	0.6977	likely_pathogenic	0.6047	pathogenic	-0.57	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/S	0.3767	ambiguous	0.3324	benign	-1.844	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
E/T	0.3799	ambiguous	0.3446	ambiguous	-1.44	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/V	0.3057	likely_benign	0.2784	benign	0.046	Stabilizing	1.0	D	0.765	deleterious	N	0.508177693	None	None	N
E/W	0.9305	likely_pathogenic	0.9081	pathogenic	0.126	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/Y	0.7234	likely_pathogenic	0.6665	pathogenic	0.215	Stabilizing	1.0	D	0.779	deleterious	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.