TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7580	22963;22964;22965	chr2:178721925;178721924;178721923	chr2:179586652;179586651;179586650
N2AB	7263	22012;22013;22014	chr2:178721925;178721924;178721923	chr2:179586652;179586651;179586650
N2A	6336	19231;19232;19233	chr2:178721925;178721924;178721923	chr2:179586652;179586651;179586650
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-60
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.4079
• 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
G/R	rs1215151938	None	0.999	N	0.814	0.29	0.362758974969	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/R	rs1215151938	None	0.999	N	0.814	0.29	0.362758974969	gnomAD-4.0.0	2.02989E-06	None	None	None	None	N	None	1.74685E-05	0	None	0	0	None	0	0	0	0	3.40298E-05

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	0.1412	likely_benign	0.1086	benign	-0.141	Destabilizing	0.273	N	0.355	neutral	N	0.398602965	None	None	N
G/C	0.4851	ambiguous	0.3662	ambiguous	-0.825	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/D	0.5856	likely_pathogenic	0.4972	ambiguous	-0.381	Destabilizing	0.996	D	0.776	deleterious	None	None	None	None	N
G/E	0.5055	ambiguous	0.4049	ambiguous	-0.541	Destabilizing	0.998	D	0.785	deleterious	N	0.308114247	None	None	N
G/F	0.7244	likely_pathogenic	0.6577	pathogenic	-0.913	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/H	0.7126	likely_pathogenic	0.6202	pathogenic	-0.294	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/I	0.3322	likely_benign	0.2412	benign	-0.353	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
G/K	0.7877	likely_pathogenic	0.708	pathogenic	-0.574	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
G/L	0.513	ambiguous	0.4004	ambiguous	-0.353	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
G/M	0.4853	ambiguous	0.3828	ambiguous	-0.468	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/N	0.4168	ambiguous	0.3255	benign	-0.243	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
G/P	0.8808	likely_pathogenic	0.8229	pathogenic	-0.254	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
G/Q	0.5712	likely_pathogenic	0.4711	ambiguous	-0.502	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
G/R	0.6857	likely_pathogenic	0.5912	pathogenic	-0.176	Destabilizing	0.999	D	0.814	deleterious	N	0.37074436	None	None	N
G/S	0.1369	likely_benign	0.1066	benign	-0.404	Destabilizing	0.592	D	0.305	neutral	None	None	None	None	N
G/T	0.2075	likely_benign	0.1522	benign	-0.492	Destabilizing	0.997	D	0.694	prob.neutral	None	None	None	None	N
G/V	0.2212	likely_benign	0.1475	benign	-0.254	Destabilizing	0.998	D	0.787	deleterious	N	0.444068683	None	None	N
G/W	0.5805	likely_pathogenic	0.5132	ambiguous	-1.048	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/Y	0.6227	likely_pathogenic	0.5364	ambiguous	-0.702	Destabilizing	1.0	D	0.834	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.