TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23791	71596;71597;71598	chr2:178574761;178574760;178574759	chr2:179439488;179439487;179439486
N2AB	22150	66673;66674;66675	chr2:178574761;178574760;178574759	chr2:179439488;179439487;179439486
N2A	21223	63892;63893;63894	chr2:178574761;178574760;178574759	chr2:179439488;179439487;179439486
N2B	14726	44401;44402;44403	chr2:178574761;178574760;178574759	chr2:179439488;179439487;179439486
Novex-1	14851	44776;44777;44778	chr2:178574761;178574760;178574759	chr2:179439488;179439487;179439486
Novex-2	14918	44977;44978;44979	chr2:178574761;178574760;178574759	chr2:179439488;179439487;179439486
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-60
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1325
• 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
L/I	rs765419522	None	0.999	D	0.828	0.774	0.80943609516	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
L/A	0.982	likely_pathogenic	0.9818	pathogenic	-2.608	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
L/C	0.9657	likely_pathogenic	0.9643	pathogenic	-2.204	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-2.424	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/E	0.9984	likely_pathogenic	0.9984	pathogenic	-2.286	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
L/F	0.8699	likely_pathogenic	0.8881	pathogenic	-1.83	Destabilizing	1.0	D	0.865	deleterious	D	0.642688435	None	None	N
L/G	0.9954	likely_pathogenic	0.9955	pathogenic	-3.081	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/H	0.9944	likely_pathogenic	0.995	pathogenic	-2.273	Highly Destabilizing	1.0	D	0.818	deleterious	D	0.659515013	None	None	N
L/I	0.5648	likely_pathogenic	0.5799	pathogenic	-1.284	Destabilizing	0.999	D	0.828	deleterious	D	0.620320266	None	None	N
L/K	0.9934	likely_pathogenic	0.9941	pathogenic	-1.914	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/M	0.5544	ambiguous	0.5529	ambiguous	-1.243	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/N	0.9971	likely_pathogenic	0.9969	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/P	0.9957	likely_pathogenic	0.9955	pathogenic	-1.702	Destabilizing	1.0	D	0.863	deleterious	D	0.643495652	None	None	N
L/Q	0.9915	likely_pathogenic	0.9912	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/R	0.9888	likely_pathogenic	0.9899	pathogenic	-1.403	Destabilizing	1.0	D	0.852	deleterious	D	0.643495652	None	None	N
L/S	0.9979	likely_pathogenic	0.9979	pathogenic	-2.848	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/T	0.9887	likely_pathogenic	0.9893	pathogenic	-2.565	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/V	0.6508	likely_pathogenic	0.6598	pathogenic	-1.702	Destabilizing	0.999	D	0.837	deleterious	D	0.581195163	None	None	N
L/W	0.9928	likely_pathogenic	0.9935	pathogenic	-1.999	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/Y	0.9909	likely_pathogenic	0.9921	pathogenic	-1.77	Destabilizing	1.0	D	0.829	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.