TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5612	17059;17060;17061	chr2:178732135;178732134;178732133	chr2:179596862;179596861;179596860
N2AB	5295	16108;16109;16110	chr2:178732135;178732134;178732133	chr2:179596862;179596861;179596860
N2A	4368	13327;13328;13329	chr2:178732135;178732134;178732133	chr2:179596862;179596861;179596860
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-39
• Domain position: 70
• Structural Position: 152
• Q(SASA): 0.2149
• Predicted PPI site: I

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
G/S	rs1060500588	None	1.0	D	0.826	0.596	0.614010665196	gnomAD-4.0.0	1.59137E-06	None	None	None	None	I	None	0	2.28655E-05	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
G/A	0.1929	likely_benign	0.2022	benign	-0.644	Destabilizing	0.974	D	0.647	neutral	D	0.583523988	None	None	I
G/C	0.4161	ambiguous	0.4366	ambiguous	-0.935	Destabilizing	1.0	D	0.781	deleterious	D	0.660177607	None	None	I
G/D	0.5943	likely_pathogenic	0.5803	pathogenic	-0.703	Destabilizing	1.0	D	0.854	deleterious	D	0.618216526	None	None	I
G/E	0.5664	likely_pathogenic	0.5452	ambiguous	-0.746	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/F	0.836	likely_pathogenic	0.8557	pathogenic	-0.973	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/H	0.7253	likely_pathogenic	0.7237	pathogenic	-1.233	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/I	0.7312	likely_pathogenic	0.7515	pathogenic	-0.23	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/K	0.6198	likely_pathogenic	0.5906	pathogenic	-0.954	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/L	0.703	likely_pathogenic	0.7225	pathogenic	-0.23	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/M	0.7328	likely_pathogenic	0.7571	pathogenic	-0.267	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/N	0.6155	likely_pathogenic	0.6219	pathogenic	-0.677	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
G/P	0.9859	likely_pathogenic	0.9882	pathogenic	-0.326	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/Q	0.5433	ambiguous	0.5265	ambiguous	-0.815	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/R	0.4168	ambiguous	0.3916	ambiguous	-0.765	Destabilizing	1.0	D	0.857	deleterious	D	0.659975803	None	None	I
G/S	0.1559	likely_benign	0.1642	benign	-1.036	Destabilizing	1.0	D	0.826	deleterious	D	0.634034083	None	None	I
G/T	0.4293	ambiguous	0.4423	ambiguous	-0.983	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
G/V	0.5693	likely_pathogenic	0.5889	pathogenic	-0.326	Destabilizing	1.0	D	0.863	deleterious	D	0.643926082	None	None	I
G/W	0.7464	likely_pathogenic	0.7731	pathogenic	-1.317	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/Y	0.7826	likely_pathogenic	0.7989	pathogenic	-0.873	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I

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.