TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24512	73759;73760;73761	chr2:178572598;178572597;178572596	chr2:179437325;179437324;179437323
N2AB	22871	68836;68837;68838	chr2:178572598;178572597;178572596	chr2:179437325;179437324;179437323
N2A	21944	66055;66056;66057	chr2:178572598;178572597;178572596	chr2:179437325;179437324;179437323
N2B	15447	46564;46565;46566	chr2:178572598;178572597;178572596	chr2:179437325;179437324;179437323
Novex-1	15572	46939;46940;46941	chr2:178572598;178572597;178572596	chr2:179437325;179437324;179437323
Novex-2	15639	47140;47141;47142	chr2:178572598;178572597;178572596	chr2:179437325;179437324;179437323
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-132
• Domain position: 82
• Structural Position: 172
• Q(SASA): 0.1476
• 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
V/I	None	None	0.058	N	0.271	0.149	0.484691182572	gnomAD-4.0.0	6.84378E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99612E-07	0	0
V/L	None	None	0.489	D	0.542	0.255	0.469496741337	gnomAD-4.0.0	6.84378E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99612E-07	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
V/A	0.894	likely_pathogenic	0.8806	pathogenic	-1.813	Destabilizing	0.014	N	0.46	neutral	N	0.488006507	None	None	I
V/C	0.9197	likely_pathogenic	0.9205	pathogenic	-1.377	Destabilizing	0.994	D	0.712	prob.delet.	None	None	None	None	I
V/D	0.9989	likely_pathogenic	0.9987	pathogenic	-2.435	Highly Destabilizing	0.97	D	0.807	deleterious	D	0.535618364	None	None	I
V/E	0.9964	likely_pathogenic	0.9958	pathogenic	-2.132	Highly Destabilizing	0.956	D	0.754	deleterious	None	None	None	None	I
V/F	0.8333	likely_pathogenic	0.7997	pathogenic	-0.986	Destabilizing	0.97	D	0.755	deleterious	D	0.529885953	None	None	I
V/G	0.9613	likely_pathogenic	0.9556	pathogenic	-2.432	Highly Destabilizing	0.89	D	0.783	deleterious	N	0.503435552	None	None	I
V/H	0.9978	likely_pathogenic	0.9975	pathogenic	-2.356	Highly Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	I
V/I	0.1086	likely_benign	0.0979	benign	-0.048	Destabilizing	0.058	N	0.271	neutral	N	0.467623986	None	None	I
V/K	0.9967	likely_pathogenic	0.996	pathogenic	-1.451	Destabilizing	0.956	D	0.76	deleterious	None	None	None	None	I
V/L	0.6894	likely_pathogenic	0.6689	pathogenic	-0.048	Destabilizing	0.489	N	0.542	neutral	D	0.534384909	None	None	I
V/M	0.7763	likely_pathogenic	0.7533	pathogenic	-0.25	Destabilizing	0.978	D	0.614	neutral	None	None	None	None	I
V/N	0.9944	likely_pathogenic	0.9937	pathogenic	-2.014	Highly Destabilizing	0.978	D	0.812	deleterious	None	None	None	None	I
V/P	0.9972	likely_pathogenic	0.9965	pathogenic	-0.611	Destabilizing	0.978	D	0.758	deleterious	None	None	None	None	I
V/Q	0.9927	likely_pathogenic	0.9919	pathogenic	-1.67	Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	I
V/R	0.9908	likely_pathogenic	0.9891	pathogenic	-1.629	Destabilizing	0.978	D	0.81	deleterious	None	None	None	None	I
V/S	0.9686	likely_pathogenic	0.9657	pathogenic	-2.639	Highly Destabilizing	0.915	D	0.745	deleterious	None	None	None	None	I
V/T	0.9189	likely_pathogenic	0.9115	pathogenic	-2.158	Highly Destabilizing	0.86	D	0.617	neutral	None	None	None	None	I
V/W	0.9974	likely_pathogenic	0.9964	pathogenic	-1.535	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	I
V/Y	0.9908	likely_pathogenic	0.9884	pathogenic	-1.092	Destabilizing	0.993	D	0.739	prob.delet.	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.