TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25523	76792;76793;76794	chr2:178569565;178569564;178569563	chr2:179434292;179434291;179434290
N2AB	23882	71869;71870;71871	chr2:178569565;178569564;178569563	chr2:179434292;179434291;179434290
N2A	22955	69088;69089;69090	chr2:178569565;178569564;178569563	chr2:179434292;179434291;179434290
N2B	16458	49597;49598;49599	chr2:178569565;178569564;178569563	chr2:179434292;179434291;179434290
Novex-1	16583	49972;49973;49974	chr2:178569565;178569564;178569563	chr2:179434292;179434291;179434290
Novex-2	16650	50173;50174;50175	chr2:178569565;178569564;178569563	chr2:179434292;179434291;179434290
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-135
• Domain position: 10
• Structural Position: 18
• Q(SASA): 0.8764
• 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
R/S	None	None	0.892	N	0.675	0.412	0.32082282376	gnomAD-4.0.0	6.84503E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99645E-07	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
R/A	0.9044	likely_pathogenic	0.9199	pathogenic	None	Stabilizing	0.845	D	0.682	prob.neutral	None	None	None	None	I
R/C	0.5164	ambiguous	0.5674	pathogenic	-0.279	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
R/D	0.977	likely_pathogenic	0.9809	pathogenic	-0.178	Destabilizing	0.975	D	0.671	neutral	None	None	None	None	I
R/E	0.866	likely_pathogenic	0.8903	pathogenic	-0.117	Destabilizing	0.845	D	0.683	prob.neutral	None	None	None	None	I
R/F	0.906	likely_pathogenic	0.927	pathogenic	-0.246	Destabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	I
R/G	0.8714	likely_pathogenic	0.8881	pathogenic	-0.18	Destabilizing	0.892	D	0.623	neutral	N	0.515433286	None	None	I
R/H	0.2723	likely_benign	0.3042	benign	-0.63	Destabilizing	0.987	D	0.663	neutral	None	None	None	None	I
R/I	0.7829	likely_pathogenic	0.8274	pathogenic	0.434	Stabilizing	0.987	D	0.689	prob.neutral	None	None	None	None	I
R/K	0.2106	likely_benign	0.2249	benign	-0.154	Destabilizing	0.025	N	0.415	neutral	N	0.475683322	None	None	I
R/L	0.6857	likely_pathogenic	0.7323	pathogenic	0.434	Stabilizing	0.916	D	0.623	neutral	None	None	None	None	I
R/M	0.7561	likely_pathogenic	0.8025	pathogenic	-0.042	Destabilizing	0.999	D	0.647	neutral	N	0.493227655	None	None	I
R/N	0.9496	likely_pathogenic	0.9575	pathogenic	-0.045	Destabilizing	0.975	D	0.649	neutral	None	None	None	None	I
R/P	0.8535	likely_pathogenic	0.8573	pathogenic	0.309	Stabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	I
R/Q	0.2939	likely_benign	0.3339	benign	-0.1	Destabilizing	0.975	D	0.647	neutral	None	None	None	None	I
R/S	0.9471	likely_pathogenic	0.9561	pathogenic	-0.33	Destabilizing	0.892	D	0.675	prob.neutral	N	0.495501698	None	None	I
R/T	0.8364	likely_pathogenic	0.8759	pathogenic	-0.141	Destabilizing	0.967	D	0.636	neutral	N	0.484958768	None	None	I
R/V	0.8242	likely_pathogenic	0.8628	pathogenic	0.309	Stabilizing	0.975	D	0.686	prob.neutral	None	None	None	None	I
R/W	0.5082	ambiguous	0.5623	ambiguous	-0.348	Destabilizing	0.999	D	0.716	prob.delet.	D	0.523448684	None	None	I
R/Y	0.7963	likely_pathogenic	0.8334	pathogenic	0.064	Stabilizing	0.996	D	0.679	prob.neutral	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.