TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28131	84616;84617;84618	chr2:178561741;178561740;178561739	chr2:179426468;179426467;179426466
N2AB	26490	79693;79694;79695	chr2:178561741;178561740;178561739	chr2:179426468;179426467;179426466
N2A	25563	76912;76913;76914	chr2:178561741;178561740;178561739	chr2:179426468;179426467;179426466
N2B	19066	57421;57422;57423	chr2:178561741;178561740;178561739	chr2:179426468;179426467;179426466
Novex-1	19191	57796;57797;57798	chr2:178561741;178561740;178561739	chr2:179426468;179426467;179426466
Novex-2	19258	57997;57998;57999	chr2:178561741;178561740;178561739	chr2:179426468;179426467;179426466
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-92
• Domain position: 77
• Structural Position: 110
• Q(SASA): 0.0664
• 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
A/T	None	None	0.992	D	0.667	0.511	0.529311486226	gnomAD-4.0.0	6.84604E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99836E-07	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
A/C	0.8581	likely_pathogenic	0.8147	pathogenic	-1.945	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
A/D	0.9978	likely_pathogenic	0.9972	pathogenic	-2.851	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
A/E	0.9946	likely_pathogenic	0.9937	pathogenic	-2.638	Highly Destabilizing	0.999	D	0.803	deleterious	D	0.582017864	None	None	N
A/F	0.9926	likely_pathogenic	0.9902	pathogenic	-0.691	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
A/G	0.5189	ambiguous	0.4837	ambiguous	-2.254	Highly Destabilizing	0.996	D	0.628	neutral	D	0.54495998	None	None	N
A/H	0.9971	likely_pathogenic	0.9963	pathogenic	-1.945	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/I	0.9729	likely_pathogenic	0.9581	pathogenic	-0.806	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
A/K	0.9986	likely_pathogenic	0.9983	pathogenic	-1.482	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
A/L	0.933	likely_pathogenic	0.8925	pathogenic	-0.806	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
A/M	0.9641	likely_pathogenic	0.9481	pathogenic	-1.364	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/N	0.9942	likely_pathogenic	0.9921	pathogenic	-1.963	Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
A/P	0.986	likely_pathogenic	0.9783	pathogenic	-1.135	Destabilizing	0.999	D	0.85	deleterious	D	0.570915048	None	None	N
A/Q	0.9881	likely_pathogenic	0.9869	pathogenic	-1.694	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/R	0.9928	likely_pathogenic	0.9927	pathogenic	-1.534	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/S	0.2848	likely_benign	0.2544	benign	-2.276	Highly Destabilizing	0.905	D	0.374	neutral	N	0.521536126	None	None	N
A/T	0.735	likely_pathogenic	0.6943	pathogenic	-1.965	Destabilizing	0.992	D	0.667	neutral	D	0.560111266	None	None	N
A/V	0.8493	likely_pathogenic	0.811	pathogenic	-1.135	Destabilizing	0.998	D	0.741	deleterious	D	0.561885693	None	None	N
A/W	0.9991	likely_pathogenic	0.9988	pathogenic	-1.216	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
A/Y	0.997	likely_pathogenic	0.9962	pathogenic	-1.02	Destabilizing	1.0	D	0.905	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.