TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27156	81691;81692;81693	chr2:178564666;178564665;178564664	chr2:179429393;179429392;179429391
N2AB	25515	76768;76769;76770	chr2:178564666;178564665;178564664	chr2:179429393;179429392;179429391
N2A	24588	73987;73988;73989	chr2:178564666;178564665;178564664	chr2:179429393;179429392;179429391
N2B	18091	54496;54497;54498	chr2:178564666;178564665;178564664	chr2:179429393;179429392;179429391
Novex-1	18216	54871;54872;54873	chr2:178564666;178564665;178564664	chr2:179429393;179429392;179429391
Novex-2	18283	55072;55073;55074	chr2:178564666;178564665;178564664	chr2:179429393;179429392;179429391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-85
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1692
• 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
G/D	None	None	0.988	D	0.825	0.629	0.474248596982	gnomAD-4.0.0	4.77582E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.29935E-05	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
G/A	0.6878	likely_pathogenic	0.6163	pathogenic	-0.818	Destabilizing	0.919	D	0.718	prob.delet.	D	0.527351661	None	None	I
G/C	0.8996	likely_pathogenic	0.8579	pathogenic	-1.01	Destabilizing	0.999	D	0.859	deleterious	D	0.547230342	None	None	I
G/D	0.991	likely_pathogenic	0.988	pathogenic	-1.628	Destabilizing	0.988	D	0.825	deleterious	D	0.546216384	None	None	I
G/E	0.9942	likely_pathogenic	0.9919	pathogenic	-1.691	Destabilizing	0.991	D	0.872	deleterious	None	None	None	None	I
G/F	0.9977	likely_pathogenic	0.997	pathogenic	-1.129	Destabilizing	0.999	D	0.908	deleterious	None	None	None	None	I
G/H	0.992	likely_pathogenic	0.989	pathogenic	-1.39	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
G/I	0.9967	likely_pathogenic	0.9948	pathogenic	-0.468	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	I
G/K	0.9976	likely_pathogenic	0.9966	pathogenic	-1.362	Destabilizing	0.991	D	0.88	deleterious	None	None	None	None	I
G/L	0.9935	likely_pathogenic	0.9906	pathogenic	-0.468	Destabilizing	0.991	D	0.891	deleterious	None	None	None	None	I
G/M	0.9956	likely_pathogenic	0.9932	pathogenic	-0.377	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	I
G/N	0.9833	likely_pathogenic	0.9756	pathogenic	-1.046	Destabilizing	0.991	D	0.823	deleterious	None	None	None	None	I
G/P	0.9991	likely_pathogenic	0.9989	pathogenic	-0.545	Destabilizing	0.995	D	0.881	deleterious	None	None	None	None	I
G/Q	0.9914	likely_pathogenic	0.9879	pathogenic	-1.276	Destabilizing	0.991	D	0.891	deleterious	None	None	None	None	I
G/R	0.9917	likely_pathogenic	0.9882	pathogenic	-0.993	Destabilizing	0.988	D	0.89	deleterious	D	0.528365619	None	None	I
G/S	0.2482	likely_benign	0.2057	benign	-1.246	Destabilizing	0.234	N	0.552	neutral	N	0.450893947	None	None	I
G/T	0.9049	likely_pathogenic	0.8611	pathogenic	-1.246	Destabilizing	0.982	D	0.863	deleterious	None	None	None	None	I
G/V	0.9912	likely_pathogenic	0.9865	pathogenic	-0.545	Destabilizing	0.988	D	0.893	deleterious	D	0.546723363	None	None	I
G/W	0.9931	likely_pathogenic	0.9912	pathogenic	-1.472	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/Y	0.9963	likely_pathogenic	0.995	pathogenic	-1.09	Destabilizing	1.0	D	0.908	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.