TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7806	23641;23642;23643	chr2:178720226;178720225;178720224	chr2:179584953;179584952;179584951
N2AB	7489	22690;22691;22692	chr2:178720226;178720225;178720224	chr2:179584953;179584952;179584951
N2A	6562	19909;19910;19911	chr2:178720226;178720225;178720224	chr2:179584953;179584952;179584951
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-63
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.6152
• 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
T/P	None	None	0.906	N	0.399	0.402	0.400468435593	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
T/A	0.066	likely_benign	0.0658	benign	-1.105	Destabilizing	0.083	N	0.272	neutral	N	0.425291787	None	None	I
T/C	0.3074	likely_benign	0.2949	benign	-0.827	Destabilizing	0.043	N	0.21	neutral	None	None	None	None	I
T/D	0.5217	ambiguous	0.5234	ambiguous	-0.749	Destabilizing	0.643	D	0.411	neutral	None	None	None	None	I
T/E	0.4213	ambiguous	0.4308	ambiguous	-0.666	Destabilizing	0.857	D	0.416	neutral	None	None	None	None	I
T/F	0.2463	likely_benign	0.2394	benign	-0.926	Destabilizing	0.987	D	0.383	neutral	None	None	None	None	I
T/G	0.2556	likely_benign	0.258	benign	-1.439	Destabilizing	0.938	D	0.359	neutral	None	None	None	None	I
T/H	0.2865	likely_benign	0.2968	benign	-1.613	Destabilizing	0.999	D	0.358	neutral	None	None	None	None	I
T/I	0.1384	likely_benign	0.1281	benign	-0.272	Destabilizing	0.019	N	0.205	neutral	N	0.502848493	None	None	I
T/K	0.2912	likely_benign	0.2984	benign	-0.784	Destabilizing	0.893	D	0.418	neutral	None	None	None	None	I
T/L	0.1072	likely_benign	0.1026	benign	-0.272	Destabilizing	0.634	D	0.294	neutral	None	None	None	None	I
T/M	0.101	likely_benign	0.0983	benign	-0.063	Destabilizing	0.967	D	0.373	neutral	None	None	None	None	I
T/N	0.1827	likely_benign	0.1852	benign	-0.992	Destabilizing	0.827	D	0.351	neutral	N	0.510824931	None	None	I
T/P	0.3824	ambiguous	0.3775	ambiguous	-0.517	Destabilizing	0.906	D	0.399	neutral	N	0.499722115	None	None	I
T/Q	0.2858	likely_benign	0.2964	benign	-1.056	Destabilizing	0.965	D	0.383	neutral	None	None	None	None	I
T/R	0.2029	likely_benign	0.2153	benign	-0.687	Destabilizing	0.994	D	0.394	neutral	None	None	None	None	I
T/S	0.1089	likely_benign	0.1097	benign	-1.312	Destabilizing	0.017	N	0.136	neutral	N	0.482457365	None	None	I
T/V	0.1025	likely_benign	0.0976	benign	-0.517	Destabilizing	0.074	N	0.13	neutral	None	None	None	None	I
T/W	0.6946	likely_pathogenic	0.6873	pathogenic	-0.866	Destabilizing	0.999	D	0.399	neutral	None	None	None	None	I
T/Y	0.3136	likely_benign	0.315	benign	-0.606	Destabilizing	0.998	D	0.382	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.