TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19321	58186;58187;58188	chr2:178594533;178594532;178594531	chr2:179459260;179459259;179459258
N2AB	17680	53263;53264;53265	chr2:178594533;178594532;178594531	chr2:179459260;179459259;179459258
N2A	16753	50482;50483;50484	chr2:178594533;178594532;178594531	chr2:179459260;179459259;179459258
N2B	10256	30991;30992;30993	chr2:178594533;178594532;178594531	chr2:179459260;179459259;179459258
Novex-1	10381	31366;31367;31368	chr2:178594533;178594532;178594531	chr2:179459260;179459259;179459258
Novex-2	10448	31567;31568;31569	chr2:178594533;178594532;178594531	chr2:179459260;179459259;179459258
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-28
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0638
• 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	rs1395371412	None	1.0	N	0.935	0.696	0.752906115721	gnomAD-4.0.0	1.5922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86E-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	0.9233	likely_pathogenic	0.9022	pathogenic	-3.057	Highly Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
L/C	0.917	likely_pathogenic	0.9135	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9994	pathogenic	-3.761	Highly Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
L/E	0.9964	likely_pathogenic	0.9949	pathogenic	-3.42	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/F	0.8667	likely_pathogenic	0.7692	pathogenic	-1.901	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/G	0.9942	likely_pathogenic	0.992	pathogenic	-3.685	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/H	0.9958	likely_pathogenic	0.9922	pathogenic	-3.334	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/I	0.0953	likely_benign	0.0848	benign	-1.152	Destabilizing	0.999	D	0.528	neutral	N	0.412289912	None	None	N
L/K	0.9949	likely_pathogenic	0.9923	pathogenic	-2.577	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
L/M	0.3918	ambiguous	0.3194	benign	-1.288	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/N	0.9972	likely_pathogenic	0.9963	pathogenic	-3.368	Highly Destabilizing	1.0	D	0.938	deleterious	None	None	None	None	N
L/P	0.9922	likely_pathogenic	0.9879	pathogenic	-1.781	Destabilizing	1.0	D	0.935	deleterious	N	0.509888835	None	None	N
L/Q	0.9913	likely_pathogenic	0.9853	pathogenic	-2.97	Highly Destabilizing	1.0	D	0.942	deleterious	N	0.52124514	None	None	N
L/R	0.9911	likely_pathogenic	0.9865	pathogenic	-2.63	Highly Destabilizing	1.0	D	0.918	deleterious	N	0.52124514	None	None	N
L/S	0.9946	likely_pathogenic	0.9914	pathogenic	-3.919	Highly Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
L/T	0.9356	likely_pathogenic	0.9127	pathogenic	-3.402	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/V	0.1031	likely_benign	0.0931	benign	-1.781	Destabilizing	0.999	D	0.544	neutral	N	0.41407385	None	None	N
L/W	0.9905	likely_pathogenic	0.9785	pathogenic	-2.246	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/Y	0.9929	likely_pathogenic	0.9855	pathogenic	-2.096	Highly Destabilizing	1.0	D	0.896	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.