TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8630	26113;26114;26115	chr2:178715526;178715525;178715524	chr2:179580253;179580252;179580251
N2AB	8313	25162;25163;25164	chr2:178715526;178715525;178715524	chr2:179580253;179580252;179580251
N2A	7386	22381;22382;22383	chr2:178715526;178715525;178715524	chr2:179580253;179580252;179580251
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-71
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.489
• 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
S/C	None	None	0.977	N	0.611	0.383	0.564651752942	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
S/A	0.1126	likely_benign	0.097	benign	-0.386	Destabilizing	0.01	N	0.438	neutral	None	None	None	None	I
S/C	0.2037	likely_benign	0.1364	benign	-0.318	Destabilizing	0.977	D	0.611	neutral	N	0.500762526	None	None	I
S/D	0.3723	ambiguous	0.2874	benign	-0.097	Destabilizing	0.41	N	0.469	neutral	None	None	None	None	I
S/E	0.4408	ambiguous	0.3665	ambiguous	-0.195	Destabilizing	0.493	N	0.462	neutral	None	None	None	None	I
S/F	0.1784	likely_benign	0.144	benign	-0.929	Destabilizing	0.949	D	0.687	prob.neutral	None	None	None	None	I
S/G	0.122	likely_benign	0.0995	benign	-0.5	Destabilizing	0.493	N	0.432	neutral	D	0.524600772	None	None	I
S/H	0.2412	likely_benign	0.2039	benign	-0.969	Destabilizing	0.986	D	0.587	neutral	None	None	None	None	I
S/I	0.1349	likely_benign	0.1116	benign	-0.213	Destabilizing	0.775	D	0.671	neutral	N	0.498040274	None	None	I
S/K	0.4079	ambiguous	0.3382	benign	-0.595	Destabilizing	0.565	D	0.458	neutral	None	None	None	None	I
S/L	0.122	likely_benign	0.101	benign	-0.213	Destabilizing	0.565	D	0.636	neutral	None	None	None	None	I
S/M	0.1835	likely_benign	0.1645	benign	0.059	Stabilizing	0.986	D	0.587	neutral	None	None	None	None	I
S/N	0.1158	likely_benign	0.0962	benign	-0.292	Destabilizing	0.058	N	0.502	neutral	N	0.497026316	None	None	I
S/P	0.7403	likely_pathogenic	0.6018	pathogenic	-0.242	Destabilizing	0.832	D	0.567	neutral	None	None	None	None	I
S/Q	0.3496	ambiguous	0.3048	benign	-0.59	Destabilizing	0.901	D	0.503	neutral	None	None	None	None	I
S/R	0.322	likely_benign	0.2614	benign	-0.304	Destabilizing	0.014	N	0.329	neutral	N	0.494215159	None	None	I
S/T	0.0772	likely_benign	0.07	benign	-0.401	Destabilizing	None	N	0.183	neutral	N	0.50183256	None	None	I
S/V	0.1647	likely_benign	0.1373	benign	-0.242	Destabilizing	0.327	N	0.599	neutral	None	None	None	None	I
S/W	0.3252	likely_benign	0.266	benign	-0.919	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	I
S/Y	0.1798	likely_benign	0.1445	benign	-0.658	Destabilizing	0.983	D	0.687	prob.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.