TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30511	91756;91757;91758	chr2:178551000;178550999;178550998	chr2:179415727;179415726;179415725
N2AB	28870	86833;86834;86835	chr2:178551000;178550999;178550998	chr2:179415727;179415726;179415725
N2A	27943	84052;84053;84054	chr2:178551000;178550999;178550998	chr2:179415727;179415726;179415725
N2B	21446	64561;64562;64563	chr2:178551000;178550999;178550998	chr2:179415727;179415726;179415725
Novex-1	21571	64936;64937;64938	chr2:178551000;178550999;178550998	chr2:179415727;179415726;179415725
Novex-2	21638	65137;65138;65139	chr2:178551000;178550999;178550998	chr2:179415727;179415726;179415725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-110
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1331
• 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
S/Y	None	None	0.999	N	0.914	0.385	0.608970947243	gnomAD-4.0.0	1.36896E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79932E-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	0.1563	likely_benign	0.1495	benign	-1.035	Destabilizing	0.994	D	0.603	neutral	N	0.426816647	None	None	N
S/C	0.26	likely_benign	0.2265	benign	-0.779	Destabilizing	1.0	D	0.823	deleterious	N	0.500199685	None	None	N
S/D	0.8732	likely_pathogenic	0.8724	pathogenic	-0.383	Destabilizing	0.998	D	0.594	neutral	None	None	None	None	N
S/E	0.9141	likely_pathogenic	0.911	pathogenic	-0.401	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
S/F	0.7545	likely_pathogenic	0.7859	pathogenic	-1.304	Destabilizing	0.999	D	0.907	deleterious	N	0.485768951	None	None	N
S/G	0.2313	likely_benign	0.2132	benign	-1.244	Destabilizing	0.998	D	0.664	prob.neutral	None	None	None	None	N
S/H	0.8003	likely_pathogenic	0.7946	pathogenic	-1.655	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
S/I	0.4707	ambiguous	0.4896	ambiguous	-0.583	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
S/K	0.965	likely_pathogenic	0.9633	pathogenic	-0.781	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
S/L	0.3379	likely_benign	0.3804	ambiguous	-0.583	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
S/M	0.4882	ambiguous	0.5331	ambiguous	-0.227	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/N	0.4145	ambiguous	0.4082	ambiguous	-0.694	Destabilizing	0.998	D	0.634	neutral	None	None	None	None	N
S/P	0.1949	likely_benign	0.1744	benign	-0.703	Destabilizing	0.999	D	0.863	deleterious	N	0.392125284	None	None	N
S/Q	0.8663	likely_pathogenic	0.8672	pathogenic	-0.951	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
S/R	0.9575	likely_pathogenic	0.9572	pathogenic	-0.586	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
S/T	0.1541	likely_benign	0.1629	benign	-0.791	Destabilizing	0.997	D	0.613	neutral	N	0.422410905	None	None	N
S/V	0.4241	ambiguous	0.4361	ambiguous	-0.703	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
S/W	0.8637	likely_pathogenic	0.8851	pathogenic	-1.18	Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
S/Y	0.6905	likely_pathogenic	0.7132	pathogenic	-0.954	Destabilizing	0.999	D	0.914	deleterious	N	0.465818468	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.