TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19710	59353;59354;59355	chr2:178592991;178592990;178592989	chr2:179457718;179457717;179457716
N2AB	18069	54430;54431;54432	chr2:178592991;178592990;178592989	chr2:179457718;179457717;179457716
N2A	17142	51649;51650;51651	chr2:178592991;178592990;178592989	chr2:179457718;179457717;179457716
N2B	10645	32158;32159;32160	chr2:178592991;178592990;178592989	chr2:179457718;179457717;179457716
Novex-1	10770	32533;32534;32535	chr2:178592991;178592990;178592989	chr2:179457718;179457717;179457716
Novex-2	10837	32734;32735;32736	chr2:178592991;178592990;178592989	chr2:179457718;179457717;179457716
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-31
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3423
• 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/N	None	None	0.801	N	0.534	0.337	0.215869574891	gnomAD-4.0.0	1.59181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43303E-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
S/A	0.1212	likely_benign	0.1246	benign	-0.46	Destabilizing	0.325	N	0.422	neutral	None	None	None	None	I
S/C	0.0959	likely_benign	0.1036	benign	-0.239	Destabilizing	0.997	D	0.619	neutral	N	0.47566488	None	None	I
S/D	0.6563	likely_pathogenic	0.6279	pathogenic	-0.007	Destabilizing	0.915	D	0.511	neutral	None	None	None	None	I
S/E	0.7464	likely_pathogenic	0.6848	pathogenic	-0.083	Destabilizing	0.915	D	0.583	neutral	None	None	None	None	I
S/F	0.5642	likely_pathogenic	0.536	ambiguous	-0.933	Destabilizing	0.991	D	0.682	prob.neutral	None	None	None	None	I
S/G	0.0671	likely_benign	0.0782	benign	-0.614	Destabilizing	0.002	N	0.279	neutral	N	0.461718655	None	None	I
S/H	0.6326	likely_pathogenic	0.5381	ambiguous	-1.138	Destabilizing	0.991	D	0.622	neutral	None	None	None	None	I
S/I	0.5414	ambiguous	0.5207	ambiguous	-0.179	Destabilizing	0.989	D	0.685	prob.neutral	N	0.492501687	None	None	I
S/K	0.8874	likely_pathogenic	0.8162	pathogenic	-0.536	Destabilizing	0.915	D	0.59	neutral	None	None	None	None	I
S/L	0.2233	likely_benign	0.2124	benign	-0.179	Destabilizing	0.915	D	0.693	prob.neutral	None	None	None	None	I
S/M	0.3525	ambiguous	0.3547	ambiguous	0.192	Stabilizing	0.998	D	0.617	neutral	None	None	None	None	I
S/N	0.3038	likely_benign	0.2875	benign	-0.265	Destabilizing	0.801	D	0.534	neutral	N	0.480322461	None	None	I
S/P	0.962	likely_pathogenic	0.9525	pathogenic	-0.242	Destabilizing	0.991	D	0.639	neutral	None	None	None	None	I
S/Q	0.688	likely_pathogenic	0.6033	pathogenic	-0.54	Destabilizing	0.991	D	0.613	neutral	None	None	None	None	I
S/R	0.842	likely_pathogenic	0.7505	pathogenic	-0.316	Destabilizing	0.966	D	0.637	neutral	N	0.483232069	None	None	I
S/T	0.2028	likely_benign	0.2049	benign	-0.367	Destabilizing	0.771	D	0.529	neutral	N	0.511632974	None	None	I
S/V	0.4865	ambiguous	0.4655	ambiguous	-0.242	Destabilizing	0.915	D	0.691	prob.neutral	None	None	None	None	I
S/W	0.6844	likely_pathogenic	0.6132	pathogenic	-0.905	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
S/Y	0.4818	ambiguous	0.4331	ambiguous	-0.64	Destabilizing	0.991	D	0.681	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.