TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35653	107182;107183;107184	chr2:178528794;178528793;178528792	chr2:179393521;179393520;179393519
N2AB	34012	102259;102260;102261	chr2:178528794;178528793;178528792	chr2:179393521;179393520;179393519
N2A	33085	99478;99479;99480	chr2:178528794;178528793;178528792	chr2:179393521;179393520;179393519
N2B	26588	79987;79988;79989	chr2:178528794;178528793;178528792	chr2:179393521;179393520;179393519
Novex-1	26713	80362;80363;80364	chr2:178528794;178528793;178528792	chr2:179393521;179393520;179393519
Novex-2	26780	80563;80564;80565	chr2:178528794;178528793;178528792	chr2:179393521;179393520;179393519
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-167
• Domain position: 47
• Structural Position: 123
• Q(SASA): 0.2456
• Predicted PPI site: N

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
Y/D	rs886042500	-2.283	0.996	N	0.801	0.599	0.631970868704	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
Y/D	rs886042500	-2.283	0.996	N	0.801	0.599	0.631970868704	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/D	rs886042500	-2.283	0.996	N	0.801	0.599	0.631970868704	gnomAD-4.0.0	2.05115E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.83268E-05	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
Y/A	0.8239	likely_pathogenic	0.8633	pathogenic	-2.346	Highly Destabilizing	0.944	D	0.651	neutral	None	None	None	None	N
Y/C	0.3891	ambiguous	0.4332	ambiguous	-1.344	Destabilizing	0.999	D	0.787	deleterious	N	0.483534801	None	None	N
Y/D	0.6983	likely_pathogenic	0.7996	pathogenic	-0.811	Destabilizing	0.996	D	0.801	deleterious	N	0.483708159	None	None	N
Y/E	0.9034	likely_pathogenic	0.9354	pathogenic	-0.677	Destabilizing	0.997	D	0.757	deleterious	None	None	None	None	N
Y/F	0.1716	likely_benign	0.16	benign	-0.947	Destabilizing	0.039	N	0.329	neutral	N	0.482321293	None	None	N
Y/G	0.7262	likely_pathogenic	0.8039	pathogenic	-2.706	Highly Destabilizing	0.992	D	0.779	deleterious	None	None	None	None	N
Y/H	0.4968	ambiguous	0.5533	ambiguous	-1.167	Destabilizing	0.996	D	0.714	prob.delet.	N	0.483534801	None	None	N
Y/I	0.7709	likely_pathogenic	0.8009	pathogenic	-1.232	Destabilizing	0.968	D	0.703	prob.neutral	None	None	None	None	N
Y/K	0.8669	likely_pathogenic	0.9119	pathogenic	-1.178	Destabilizing	0.992	D	0.757	deleterious	None	None	None	None	N
Y/L	0.6626	likely_pathogenic	0.7125	pathogenic	-1.232	Destabilizing	0.895	D	0.523	neutral	None	None	None	None	N
Y/M	0.8454	likely_pathogenic	0.8687	pathogenic	-1.065	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
Y/N	0.4602	ambiguous	0.5503	ambiguous	-1.534	Destabilizing	0.996	D	0.781	deleterious	N	0.483534801	None	None	N
Y/P	0.8937	likely_pathogenic	0.94	pathogenic	-1.602	Destabilizing	0.997	D	0.809	deleterious	None	None	None	None	N
Y/Q	0.8519	likely_pathogenic	0.8977	pathogenic	-1.392	Destabilizing	0.997	D	0.769	deleterious	None	None	None	None	N
Y/R	0.7607	likely_pathogenic	0.8341	pathogenic	-0.872	Destabilizing	0.992	D	0.783	deleterious	None	None	None	None	N
Y/S	0.5214	ambiguous	0.6155	pathogenic	-2.227	Highly Destabilizing	0.989	D	0.751	deleterious	N	0.483014726	None	None	N
Y/T	0.7684	likely_pathogenic	0.8202	pathogenic	-1.985	Destabilizing	0.992	D	0.757	deleterious	None	None	None	None	N
Y/V	0.6911	likely_pathogenic	0.7326	pathogenic	-1.602	Destabilizing	0.895	D	0.652	neutral	None	None	None	None	N
Y/W	0.6047	likely_pathogenic	0.6201	pathogenic	-0.414	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N

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.