TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3115	9568;9569;9570	chr2:178767887;178767886;178767885	chr2:179632614;179632613;179632612
N2AB	3115	9568;9569;9570	chr2:178767887;178767886;178767885	chr2:179632614;179632613;179632612
N2A	3115	9568;9569;9570	chr2:178767887;178767886;178767885	chr2:179632614;179632613;179632612
N2B	3069	9430;9431;9432	chr2:178767887;178767886;178767885	chr2:179632614;179632613;179632612
Novex-1	3069	9430;9431;9432	chr2:178767887;178767886;178767885	chr2:179632614;179632613;179632612
Novex-2	3069	9430;9431;9432	chr2:178767887;178767886;178767885	chr2:179632614;179632613;179632612
Novex-3	3115	9568;9569;9570	chr2:178767887;178767886;178767885	chr2:179632614;179632613;179632612

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-21
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.1769
• 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/R	rs773714030	-1.688	0.484	N	0.576	0.461	0.731167935182	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	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	0.4218	ambiguous	0.6084	pathogenic	-2.464	Highly Destabilizing	0.035	N	0.525	neutral	None	None	None	None	N
L/C	0.5861	likely_pathogenic	0.7334	pathogenic	-1.585	Destabilizing	0.935	D	0.598	neutral	None	None	None	None	N
L/D	0.9188	likely_pathogenic	0.9596	pathogenic	-2.604	Highly Destabilizing	0.791	D	0.604	neutral	None	None	None	None	N
L/E	0.693	likely_pathogenic	0.8153	pathogenic	-2.468	Highly Destabilizing	0.555	D	0.621	neutral	None	None	None	None	N
L/F	0.1578	likely_benign	0.2307	benign	-1.482	Destabilizing	0.001	N	0.449	neutral	None	None	None	None	N
L/G	0.8167	likely_pathogenic	0.9108	pathogenic	-2.922	Highly Destabilizing	0.262	N	0.608	neutral	None	None	None	None	N
L/H	0.2892	likely_benign	0.4609	ambiguous	-2.279	Highly Destabilizing	0.824	D	0.618	neutral	None	None	None	None	N
L/I	0.0885	likely_benign	0.1224	benign	-1.179	Destabilizing	0.001	N	0.288	neutral	None	None	None	None	N
L/K	0.6644	likely_pathogenic	0.7747	pathogenic	-2.052	Highly Destabilizing	0.262	N	0.6	neutral	None	None	None	None	N
L/M	0.1063	likely_benign	0.1496	benign	-0.952	Destabilizing	0.005	N	0.318	neutral	N	0.452318985	None	None	N
L/N	0.5288	ambiguous	0.7137	pathogenic	-2.101	Highly Destabilizing	0.791	D	0.599	neutral	None	None	None	None	N
L/P	0.9842	likely_pathogenic	0.9877	pathogenic	-1.586	Destabilizing	0.741	D	0.6	neutral	D	0.551233173	None	None	N
L/Q	0.2611	likely_benign	0.4093	ambiguous	-2.114	Highly Destabilizing	0.484	N	0.571	neutral	N	0.470655251	None	None	N
L/R	0.5312	ambiguous	0.64	pathogenic	-1.527	Destabilizing	0.484	N	0.576	neutral	N	0.465285128	None	None	N
L/S	0.4167	ambiguous	0.6516	pathogenic	-2.732	Highly Destabilizing	0.262	N	0.566	neutral	None	None	None	None	N
L/T	0.3221	likely_benign	0.5216	ambiguous	-2.48	Highly Destabilizing	0.149	N	0.589	neutral	None	None	None	None	N
L/V	0.1081	likely_benign	0.1511	benign	-1.586	Destabilizing	None	N	0.278	neutral	N	0.392400723	None	None	N
L/W	0.3295	likely_benign	0.4556	ambiguous	-1.807	Destabilizing	0.824	D	0.588	neutral	None	None	None	None	N
L/Y	0.3934	ambiguous	0.5447	ambiguous	-1.581	Destabilizing	0.235	N	0.625	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.