TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14146	42661;42662;42663	chr2:178634063;178634062;178634061	chr2:179498790;179498789;179498788
N2AB	12505	37738;37739;37740	chr2:178634063;178634062;178634061	chr2:179498790;179498789;179498788
N2A	11578	34957;34958;34959	chr2:178634063;178634062;178634061	chr2:179498790;179498789;179498788
N2B	5081	15466;15467;15468	chr2:178634063;178634062;178634061	chr2:179498790;179498789;179498788
Novex-1	5206	15841;15842;15843	chr2:178634063;178634062;178634061	chr2:179498790;179498789;179498788
Novex-2	5273	16042;16043;16044	chr2:178634063;178634062;178634061	chr2:179498790;179498789;179498788
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-92
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2007
• 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/L	rs760628135	0.261	0.012	N	0.341	0.262	0.312001716656	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
S/L	rs760628135	0.261	0.012	N	0.341	0.262	0.312001716656	gnomAD-4.0.0	1.59317E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86094E-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	0.0858	likely_benign	0.0988	benign	-0.47	Destabilizing	0.454	N	0.337	neutral	N	0.508560084	None	None	N
S/C	0.1244	likely_benign	0.1399	benign	-0.35	Destabilizing	0.998	D	0.397	neutral	None	None	None	None	N
S/D	0.3141	likely_benign	0.3429	ambiguous	-0.059	Destabilizing	0.842	D	0.358	neutral	None	None	None	None	N
S/E	0.3227	likely_benign	0.3671	ambiguous	-0.096	Destabilizing	0.728	D	0.337	neutral	None	None	None	None	N
S/F	0.1622	likely_benign	0.177	benign	-0.697	Destabilizing	0.949	D	0.478	neutral	None	None	None	None	N
S/G	0.1434	likely_benign	0.1652	benign	-0.687	Destabilizing	0.842	D	0.341	neutral	None	None	None	None	N
S/H	0.163	likely_benign	0.1973	benign	-1.155	Destabilizing	0.993	D	0.39	neutral	None	None	None	None	N
S/I	0.1131	likely_benign	0.1384	benign	-0.015	Destabilizing	0.904	D	0.436	neutral	None	None	None	None	N
S/K	0.2491	likely_benign	0.3026	benign	-0.687	Destabilizing	0.067	N	0.241	neutral	None	None	None	None	N
S/L	0.08	likely_benign	0.0913	benign	-0.015	Destabilizing	0.012	N	0.341	neutral	N	0.506612423	None	None	N
S/M	0.1508	likely_benign	0.1743	benign	0.18	Stabilizing	0.949	D	0.395	neutral	None	None	None	None	N
S/N	0.0974	likely_benign	0.1106	benign	-0.522	Destabilizing	0.842	D	0.394	neutral	None	None	None	None	N
S/P	0.7204	likely_pathogenic	0.7942	pathogenic	-0.133	Destabilizing	0.966	D	0.365	neutral	D	0.531992812	None	None	N
S/Q	0.2645	likely_benign	0.3202	benign	-0.699	Destabilizing	0.325	N	0.231	neutral	None	None	None	None	N
S/R	0.2289	likely_benign	0.2901	benign	-0.512	Destabilizing	0.728	D	0.337	neutral	None	None	None	None	N
S/T	0.0621	likely_benign	0.07	benign	-0.562	Destabilizing	0.051	N	0.241	neutral	N	0.468423264	None	None	N
S/V	0.1264	likely_benign	0.1544	benign	-0.133	Destabilizing	0.728	D	0.399	neutral	None	None	None	None	N
S/W	0.2841	likely_benign	0.3274	benign	-0.697	Destabilizing	0.998	D	0.559	neutral	None	None	None	None	N
S/Y	0.1285	likely_benign	0.1413	benign	-0.44	Destabilizing	0.991	D	0.479	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.