TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5430	16513;16514;16515	chr2:178732888;178732887;178732886	chr2:179597615;179597614;179597613
N2AB	5113	15562;15563;15564	chr2:178732888;178732887;178732886	chr2:179597615;179597614;179597613
N2A	4186	12781;12782;12783	chr2:178732888;178732887;178732886	chr2:179597615;179597614;179597613
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: R
• RefSeq wild type transcript codon: CGA
• RefSeq wild type template codon: GCT
• Domain: Ig-37
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.4849
• 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
R/Q	rs746130933	-0.744	0.175	N	0.358	0.244	0.18274738541	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.68275E-04	None	0	None	0	0	0
R/Q	rs746130933	-0.744	0.175	N	0.358	0.244	0.18274738541	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/Q	rs746130933	-0.744	0.175	N	0.358	0.244	0.18274738541	gnomAD-4.0.0	3.71924E-06	None	None	None	None	I	None	0	0	None	0	4.46768E-05	None	0	0	2.5432E-06	1.09868E-05	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
R/A	0.5307	ambiguous	0.5202	ambiguous	-1.527	Destabilizing	0.447	N	0.556	neutral	None	None	None	None	I
R/C	0.2014	likely_benign	0.1891	benign	-1.574	Destabilizing	0.992	D	0.629	neutral	None	None	None	None	I
R/D	0.8939	likely_pathogenic	0.8866	pathogenic	-0.553	Destabilizing	0.617	D	0.647	neutral	None	None	None	None	I
R/E	0.4393	ambiguous	0.4548	ambiguous	-0.438	Destabilizing	0.25	N	0.558	neutral	None	None	None	None	I
R/F	0.6451	likely_pathogenic	0.6454	pathogenic	-1.475	Destabilizing	0.92	D	0.622	neutral	None	None	None	None	I
R/G	0.5001	ambiguous	0.4676	ambiguous	-1.811	Destabilizing	0.756	D	0.609	neutral	N	0.50006451	None	None	I
R/H	0.1092	likely_benign	0.1027	benign	-1.837	Destabilizing	0.012	N	0.349	neutral	None	None	None	None	I
R/I	0.3404	ambiguous	0.3457	ambiguous	-0.753	Destabilizing	0.92	D	0.629	neutral	None	None	None	None	I
R/K	0.1105	likely_benign	0.108	benign	-1.524	Destabilizing	0.009	N	0.253	neutral	None	None	None	None	I
R/L	0.3295	likely_benign	0.325	benign	-0.753	Destabilizing	0.756	D	0.623	neutral	N	0.489076694	None	None	I
R/M	0.3509	ambiguous	0.3484	ambiguous	-0.894	Destabilizing	0.92	D	0.599	neutral	None	None	None	None	I
R/N	0.7385	likely_pathogenic	0.7229	pathogenic	-0.91	Destabilizing	0.617	D	0.595	neutral	None	None	None	None	I
R/P	0.9848	likely_pathogenic	0.9843	pathogenic	-0.994	Destabilizing	0.957	D	0.649	neutral	N	0.511838889	None	None	I
R/Q	0.1015	likely_benign	0.0982	benign	-1.195	Destabilizing	0.175	N	0.358	neutral	N	0.486188317	None	None	I
R/S	0.5631	ambiguous	0.5428	ambiguous	-1.86	Destabilizing	0.447	N	0.591	neutral	None	None	None	None	I
R/T	0.2771	likely_benign	0.2698	benign	-1.569	Destabilizing	0.617	D	0.591	neutral	None	None	None	None	I
R/V	0.3981	ambiguous	0.4049	ambiguous	-0.994	Destabilizing	0.85	D	0.645	neutral	None	None	None	None	I
R/W	0.3187	likely_benign	0.3206	benign	-1.001	Destabilizing	0.992	D	0.653	neutral	None	None	None	None	I
R/Y	0.5259	ambiguous	0.5205	ambiguous	-0.736	Destabilizing	0.85	D	0.643	neutral	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.