TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20919	62980;62981;62982	chr2:178588970;178588969;178588968	chr2:179453697;179453696;179453695
N2AB	19278	58057;58058;58059	chr2:178588970;178588969;178588968	chr2:179453697;179453696;179453695
N2A	18351	55276;55277;55278	chr2:178588970;178588969;178588968	chr2:179453697;179453696;179453695
N2B	11854	35785;35786;35787	chr2:178588970;178588969;178588968	chr2:179453697;179453696;179453695
Novex-1	11979	36160;36161;36162	chr2:178588970;178588969;178588968	chr2:179453697;179453696;179453695
Novex-2	12046	36361;36362;36363	chr2:178588970;178588969;178588968	chr2:179453697;179453696;179453695
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-39
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.9338
• 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
L/S	rs756059826	-0.385	0.966	N	0.399	0.32	0.713529394019	gnomAD-2.1.1	8.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
L/S	rs756059826	-0.385	0.966	N	0.399	0.32	0.713529394019	gnomAD-4.0.0	1.59424E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86107E-06	0	0
L/W	None	None	0.028	N	0.359	0.176	0.670941187113	gnomAD-4.0.0	1.59424E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86107E-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
L/A	0.211	likely_benign	0.1747	benign	-0.689	Destabilizing	0.842	D	0.412	neutral	None	None	None	None	N
L/C	0.5201	ambiguous	0.4581	ambiguous	-0.657	Destabilizing	0.998	D	0.437	neutral	None	None	None	None	N
L/D	0.6945	likely_pathogenic	0.6028	pathogenic	-0.061	Destabilizing	0.991	D	0.413	neutral	None	None	None	None	N
L/E	0.3886	ambiguous	0.3049	benign	-0.142	Destabilizing	0.991	D	0.413	neutral	None	None	None	None	N
L/F	0.1691	likely_benign	0.141	benign	-0.629	Destabilizing	0.934	D	0.42	neutral	N	0.443829114	None	None	N
L/G	0.4715	ambiguous	0.4088	ambiguous	-0.868	Destabilizing	0.974	D	0.381	neutral	None	None	None	None	N
L/H	0.2784	likely_benign	0.226	benign	-0.135	Destabilizing	0.998	D	0.405	neutral	None	None	None	None	N
L/I	0.0808	likely_benign	0.0727	benign	-0.337	Destabilizing	0.016	N	0.168	neutral	None	None	None	None	N
L/K	0.27	likely_benign	0.2164	benign	-0.371	Destabilizing	0.974	D	0.419	neutral	None	None	None	None	N
L/M	0.0988	likely_benign	0.0899	benign	-0.388	Destabilizing	0.934	D	0.487	neutral	N	0.448677574	None	None	N
L/N	0.3358	likely_benign	0.2704	benign	-0.188	Destabilizing	0.991	D	0.411	neutral	None	None	None	None	N
L/P	0.2204	likely_benign	0.1873	benign	-0.421	Destabilizing	0.991	D	0.409	neutral	None	None	None	None	N
L/Q	0.1575	likely_benign	0.1269	benign	-0.393	Destabilizing	0.991	D	0.423	neutral	None	None	None	None	N
L/R	0.2385	likely_benign	0.2002	benign	0.165	Stabilizing	0.991	D	0.423	neutral	None	None	None	None	N
L/S	0.2727	likely_benign	0.2174	benign	-0.682	Destabilizing	0.966	D	0.399	neutral	N	0.393205506	None	None	N
L/T	0.1797	likely_benign	0.1464	benign	-0.651	Destabilizing	0.842	D	0.437	neutral	None	None	None	None	N
L/V	0.0827	likely_benign	0.075	benign	-0.421	Destabilizing	0.022	N	0.132	neutral	N	0.383991377	None	None	N
L/W	0.3791	ambiguous	0.3262	benign	-0.642	Destabilizing	0.028	N	0.359	neutral	N	0.492217707	None	None	N
L/Y	0.415	ambiguous	0.3633	ambiguous	-0.395	Destabilizing	0.949	D	0.434	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.