TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5611	17056;17057;17058	chr2:178732138;178732137;178732136	chr2:179596865;179596864;179596863
N2AB	5294	16105;16106;16107	chr2:178732138;178732137;178732136	chr2:179596865;179596864;179596863
N2A	4367	13324;13325;13326	chr2:178732138;178732137;178732136	chr2:179596865;179596864;179596863
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-39
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.2586
• 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/R	rs775946529	-0.264	1.0	N	0.871	0.438	0.644143578622	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
S/R	rs775946529	-0.264	1.0	N	0.871	0.438	0.644143578622	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	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	0.0923	likely_benign	0.1048	benign	-0.8	Destabilizing	0.998	D	0.431	neutral	None	None	None	None	N
S/C	0.1619	likely_benign	0.2235	benign	-0.515	Destabilizing	1.0	D	0.853	deleterious	D	0.5371753	None	None	N
S/D	0.5608	ambiguous	0.5652	pathogenic	-0.064	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
S/E	0.6906	likely_pathogenic	0.7056	pathogenic	-0.079	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
S/F	0.3999	ambiguous	0.4737	ambiguous	-1.056	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
S/G	0.0874	likely_benign	0.1016	benign	-1.024	Destabilizing	0.999	D	0.529	neutral	N	0.489988878	None	None	N
S/H	0.5897	likely_pathogenic	0.6304	pathogenic	-1.503	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
S/I	0.3294	likely_benign	0.3752	ambiguous	-0.312	Destabilizing	1.0	D	0.875	deleterious	N	0.518564066	None	None	N
S/K	0.8044	likely_pathogenic	0.8323	pathogenic	-0.625	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
S/L	0.1564	likely_benign	0.1849	benign	-0.312	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
S/M	0.2857	likely_benign	0.3301	benign	0.009	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
S/N	0.2291	likely_benign	0.2287	benign	-0.545	Destabilizing	0.999	D	0.563	neutral	N	0.50290212	None	None	N
S/P	0.7293	likely_pathogenic	0.8042	pathogenic	-0.443	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/Q	0.6803	likely_pathogenic	0.7099	pathogenic	-0.731	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
S/R	0.6755	likely_pathogenic	0.7245	pathogenic	-0.524	Destabilizing	1.0	D	0.871	deleterious	N	0.519525118	None	None	N
S/T	0.0918	likely_benign	0.0962	benign	-0.625	Destabilizing	0.999	D	0.491	neutral	N	0.508529246	None	None	N
S/V	0.3332	likely_benign	0.3885	ambiguous	-0.443	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
S/W	0.5852	likely_pathogenic	0.6632	pathogenic	-0.994	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
S/Y	0.3677	ambiguous	0.4146	ambiguous	-0.74	Destabilizing	1.0	D	0.901	deleterious	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.