TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8560	25903;25904;25905	chr2:178715736;178715735;178715734	chr2:179580463;179580462;179580461
N2AB	8243	24952;24953;24954	chr2:178715736;178715735;178715734	chr2:179580463;179580462;179580461
N2A	7316	22171;22172;22173	chr2:178715736;178715735;178715734	chr2:179580463;179580462;179580461
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-71
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.425
• 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
I/T	rs727504204	None	None	N	0.085	0.184	0.611125358375	gnomAD-4.0.0	1.38592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.07777E-07	1.19474E-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
I/A	0.1766	likely_benign	0.2003	benign	-0.968	Destabilizing	0.088	N	0.174	neutral	None	None	None	None	I
I/C	0.6491	likely_pathogenic	0.6947	pathogenic	-0.782	Destabilizing	0.884	D	0.307	neutral	None	None	None	None	I
I/D	0.5226	ambiguous	0.5577	ambiguous	-0.502	Destabilizing	0.517	D	0.436	neutral	None	None	None	None	I
I/E	0.3893	ambiguous	0.4268	ambiguous	-0.548	Destabilizing	0.441	N	0.405	neutral	None	None	None	None	I
I/F	0.1362	likely_benign	0.1518	benign	-0.67	Destabilizing	None	N	0.067	neutral	N	0.495309233	None	None	I
I/G	0.5102	ambiguous	0.5684	pathogenic	-1.204	Destabilizing	0.517	D	0.381	neutral	None	None	None	None	I
I/H	0.4011	ambiguous	0.4466	ambiguous	-0.36	Destabilizing	0.906	D	0.335	neutral	None	None	None	None	I
I/K	0.3252	likely_benign	0.3702	ambiguous	-0.73	Destabilizing	0.031	N	0.402	neutral	None	None	None	None	I
I/L	0.1011	likely_benign	0.1068	benign	-0.435	Destabilizing	None	N	0.078	neutral	N	0.4564442	None	None	I
I/M	0.0843	likely_benign	0.0887	benign	-0.512	Destabilizing	0.253	N	0.261	neutral	N	0.488997693	None	None	I
I/N	0.1825	likely_benign	0.1983	benign	-0.558	Destabilizing	0.447	N	0.457	neutral	N	0.514278995	None	None	I
I/P	0.5905	likely_pathogenic	0.6446	pathogenic	-0.58	Destabilizing	0.884	D	0.443	neutral	None	None	None	None	I
I/Q	0.3387	likely_benign	0.3816	ambiguous	-0.746	Destabilizing	0.759	D	0.401	neutral	None	None	None	None	I
I/R	0.2498	likely_benign	0.2927	benign	-0.134	Destabilizing	0.599	D	0.438	neutral	None	None	None	None	I
I/S	0.1803	likely_benign	0.2019	benign	-1.059	Destabilizing	0.143	N	0.223	neutral	N	0.50675559	None	None	I
I/T	0.0805	likely_benign	0.0886	benign	-0.992	Destabilizing	None	N	0.085	neutral	N	0.4723923	None	None	I
I/V	0.0677	likely_benign	0.0674	benign	-0.58	Destabilizing	None	N	0.074	neutral	N	0.440549241	None	None	I
I/W	0.6375	likely_pathogenic	0.6924	pathogenic	-0.701	Destabilizing	0.992	D	0.323	neutral	None	None	None	None	I
I/Y	0.4121	ambiguous	0.4462	ambiguous	-0.484	Destabilizing	0.024	N	0.314	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.