TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24704	74335;74336;74337	chr2:178572022;178572021;178572020	chr2:179436749;179436748;179436747
N2AB	23063	69412;69413;69414	chr2:178572022;178572021;178572020	chr2:179436749;179436748;179436747
N2A	22136	66631;66632;66633	chr2:178572022;178572021;178572020	chr2:179436749;179436748;179436747
N2B	15639	47140;47141;47142	chr2:178572022;178572021;178572020	chr2:179436749;179436748;179436747
Novex-1	15764	47515;47516;47517	chr2:178572022;178572021;178572020	chr2:179436749;179436748;179436747
Novex-2	15831	47716;47717;47718	chr2:178572022;178572021;178572020	chr2:179436749;179436748;179436747
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: Fn3-67
• Domain position: 89
• Structural Position: 124
• Q(SASA): 0.437
• 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/R	rs397517697	None	0.965	N	0.813	0.279	0.242825505644	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/R	rs397517697	None	0.965	N	0.813	0.279	0.242825505644	gnomAD-4.0.0	6.578E-06	None	None	None	None	I	None	2.41476E-05	0	None	0	0	None	0	0	0	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	0.0782	likely_benign	0.077	benign	-0.104	Destabilizing	0.041	N	0.571	neutral	None	None	None	None	I
S/C	0.14	likely_benign	0.1441	benign	-0.6	Destabilizing	0.994	D	0.731	deleterious	N	0.475986686	None	None	I
S/D	0.546	ambiguous	0.5661	pathogenic	-0.14	Destabilizing	0.737	D	0.737	deleterious	None	None	None	None	I
S/E	0.6778	likely_pathogenic	0.6951	pathogenic	-0.237	Destabilizing	0.797	D	0.724	deleterious	None	None	None	None	I
S/F	0.4041	ambiguous	0.4246	ambiguous	-0.872	Destabilizing	0.987	D	0.738	deleterious	None	None	None	None	I
S/G	0.057	likely_benign	0.0553	benign	-0.138	Destabilizing	0.005	N	0.304	neutral	N	0.468396698	None	None	I
S/H	0.4862	ambiguous	0.5024	ambiguous	-0.355	Destabilizing	0.999	D	0.727	deleterious	None	None	None	None	I
S/I	0.199	likely_benign	0.2124	benign	-0.143	Destabilizing	0.965	D	0.769	deleterious	N	0.514531633	None	None	I
S/K	0.8098	likely_pathogenic	0.8225	pathogenic	-0.478	Destabilizing	0.913	D	0.716	prob.delet.	None	None	None	None	I
S/L	0.1439	likely_benign	0.1539	benign	-0.143	Destabilizing	0.84	D	0.731	deleterious	None	None	None	None	I
S/M	0.2212	likely_benign	0.2284	benign	-0.345	Destabilizing	0.999	D	0.723	deleterious	None	None	None	None	I
S/N	0.1431	likely_benign	0.1498	benign	-0.338	Destabilizing	0.199	N	0.743	deleterious	N	0.468162326	None	None	I
S/P	0.1975	likely_benign	0.2196	benign	-0.107	Destabilizing	0.952	D	0.802	deleterious	None	None	None	None	I
S/Q	0.5852	likely_pathogenic	0.5983	pathogenic	-0.515	Destabilizing	0.987	D	0.783	deleterious	None	None	None	None	I
S/R	0.7375	likely_pathogenic	0.751	pathogenic	-0.193	Destabilizing	0.965	D	0.813	deleterious	N	0.489860979	None	None	I
S/T	0.0946	likely_benign	0.0999	benign	-0.409	Destabilizing	0.001	N	0.431	neutral	N	0.482998004	None	None	I
S/V	0.204	likely_benign	0.2146	benign	-0.107	Destabilizing	0.873	D	0.731	deleterious	None	None	None	None	I
S/W	0.5403	ambiguous	0.5558	ambiguous	-1.007	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
S/Y	0.3652	ambiguous	0.3767	ambiguous	-0.671	Destabilizing	0.996	D	0.727	deleterious	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.