TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5132	15619;15620;15621	chr2:178734430;178734429;178734428	chr2:179599157;179599156;179599155
N2AB	4815	14668;14669;14670	chr2:178734430;178734429;178734428	chr2:179599157;179599156;179599155
N2A	3888	11887;11888;11889	chr2:178734430;178734429;178734428	chr2:179599157;179599156;179599155
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-34
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0592
• 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/P	None	None	1.0	D	0.918	0.922	0.945249901596	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85863E-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	0.7862	likely_pathogenic	0.8409	pathogenic	-2.581	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
L/C	0.8332	likely_pathogenic	0.8814	pathogenic	-1.632	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.399	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/E	0.9936	likely_pathogenic	0.9948	pathogenic	-3.098	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/F	0.4499	ambiguous	0.5917	pathogenic	-1.7	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/G	0.9673	likely_pathogenic	0.9784	pathogenic	-3.119	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/H	0.9824	likely_pathogenic	0.9877	pathogenic	-2.92	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/I	0.17	likely_benign	0.1993	benign	-0.944	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
L/K	0.9926	likely_pathogenic	0.9931	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/M	0.1477	likely_benign	0.1878	benign	-1.051	Destabilizing	1.0	D	0.791	deleterious	D	0.692356895	None	None	N
L/N	0.9941	likely_pathogenic	0.9958	pathogenic	-2.902	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/P	0.994	likely_pathogenic	0.9954	pathogenic	-1.485	Destabilizing	1.0	D	0.918	deleterious	D	0.797220495	None	None	N
L/Q	0.9624	likely_pathogenic	0.9684	pathogenic	-2.523	Highly Destabilizing	1.0	D	0.921	deleterious	D	0.797220495	None	None	N
L/R	0.9825	likely_pathogenic	0.9831	pathogenic	-2.272	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.797220495	None	None	N
L/S	0.9682	likely_pathogenic	0.9795	pathogenic	-3.282	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/T	0.8821	likely_pathogenic	0.9142	pathogenic	-2.829	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/V	0.1606	likely_benign	0.1972	benign	-1.485	Destabilizing	0.999	D	0.643	neutral	D	0.722701596	None	None	N
L/W	0.9371	likely_pathogenic	0.9571	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/Y	0.9587	likely_pathogenic	0.9729	pathogenic	-1.878	Destabilizing	1.0	D	0.873	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.