TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2877	8854;8855;8856	chr2:178770072;178770071;178770070	chr2:179634799;179634798;179634797
N2AB	2877	8854;8855;8856	chr2:178770072;178770071;178770070	chr2:179634799;179634798;179634797
N2A	2877	8854;8855;8856	chr2:178770072;178770071;178770070	chr2:179634799;179634798;179634797
N2B	2831	8716;8717;8718	chr2:178770072;178770071;178770070	chr2:179634799;179634798;179634797
Novex-1	2831	8716;8717;8718	chr2:178770072;178770071;178770070	chr2:179634799;179634798;179634797
Novex-2	2831	8716;8717;8718	chr2:178770072;178770071;178770070	chr2:179634799;179634798;179634797
Novex-3	2877	8854;8855;8856	chr2:178770072;178770071;178770070	chr2:179634799;179634798;179634797

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-18
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.0894
• 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/R	None	None	1.0	D	0.918	0.676	0.82818415665	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9566	likely_pathogenic	0.9622	pathogenic	-2.812	Highly Destabilizing	0.997	D	0.75	deleterious	None	None	None	None	N
L/C	0.9347	likely_pathogenic	0.9416	pathogenic	-1.774	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.426	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
L/E	0.999	likely_pathogenic	0.9987	pathogenic	-3.094	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/F	0.9329	likely_pathogenic	0.929	pathogenic	-1.7	Destabilizing	0.538	D	0.44	neutral	None	None	None	None	N
L/G	0.9945	likely_pathogenic	0.9946	pathogenic	-3.428	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
L/H	0.9975	likely_pathogenic	0.9968	pathogenic	-3.137	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/I	0.2771	likely_benign	0.2986	benign	-0.946	Destabilizing	0.994	D	0.581	neutral	None	None	None	None	N
L/K	0.9986	likely_pathogenic	0.9977	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
L/M	0.5883	likely_pathogenic	0.602	pathogenic	-1.038	Destabilizing	1.0	D	0.809	deleterious	D	0.677741753	None	None	N
L/N	0.9983	likely_pathogenic	0.9978	pathogenic	-2.789	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
L/P	0.999	likely_pathogenic	0.9987	pathogenic	-1.561	Destabilizing	1.0	D	0.923	deleterious	D	0.717937041	None	None	N
L/Q	0.9963	likely_pathogenic	0.9957	pathogenic	-2.41	Highly Destabilizing	1.0	D	0.924	deleterious	D	0.717937041	None	None	N
L/R	0.9957	likely_pathogenic	0.994	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.918	deleterious	D	0.717937041	None	None	N
L/S	0.9972	likely_pathogenic	0.997	pathogenic	-3.326	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/T	0.9806	likely_pathogenic	0.9797	pathogenic	-2.828	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/V	0.2736	likely_benign	0.3099	benign	-1.561	Destabilizing	0.992	D	0.585	neutral	D	0.582691199	None	None	N
L/W	0.9966	likely_pathogenic	0.9956	pathogenic	-2.097	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/Y	0.9926	likely_pathogenic	0.9915	pathogenic	-1.902	Destabilizing	0.996	D	0.884	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.