TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2260	7003;7004;7005	chr2:178774933;178774932;178774931	chr2:179639660;179639659;179639658
N2AB	2260	7003;7004;7005	chr2:178774933;178774932;178774931	chr2:179639660;179639659;179639658
N2A	2260	7003;7004;7005	chr2:178774933;178774932;178774931	chr2:179639660;179639659;179639658
N2B	2214	6865;6866;6867	chr2:178774933;178774932;178774931	chr2:179639660;179639659;179639658
Novex-1	2214	6865;6866;6867	chr2:178774933;178774932;178774931	chr2:179639660;179639659;179639658
Novex-2	2214	6865;6866;6867	chr2:178774933;178774932;178774931	chr2:179639660;179639659;179639658
Novex-3	2260	7003;7004;7005	chr2:178774933;178774932;178774931	chr2:179639660;179639659;179639658

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-11
• Domain position: 87
• Structural Position: 174
• Q(SASA): 0.1062
• 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	rs370058135	-0.877	0.999	D	0.573	0.624	None	gnomAD-2.1.1	2E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.42E-05	0
L/I	rs370058135	-0.877	0.999	D	0.573	0.624	None	gnomAD-4.0.0	4.78987E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29589E-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	0.9567	likely_pathogenic	0.9522	pathogenic	-2.804	Highly Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
L/C	0.9176	likely_pathogenic	0.9134	pathogenic	-1.825	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.502	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/E	0.9981	likely_pathogenic	0.998	pathogenic	-3.19	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
L/F	0.8083	likely_pathogenic	0.8025	pathogenic	-1.751	Destabilizing	1.0	D	0.831	deleterious	D	0.683276039	None	None	N
L/G	0.9909	likely_pathogenic	0.9903	pathogenic	-3.406	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/H	0.9939	likely_pathogenic	0.9935	pathogenic	-3.055	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.755415398	None	None	N
L/I	0.2837	likely_benign	0.2745	benign	-1.001	Destabilizing	0.999	D	0.573	neutral	D	0.653860452	None	None	N
L/K	0.996	likely_pathogenic	0.9957	pathogenic	-2.258	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/M	0.403	ambiguous	0.3932	ambiguous	-0.945	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/N	0.9967	likely_pathogenic	0.9965	pathogenic	-2.927	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/P	0.9988	likely_pathogenic	0.9987	pathogenic	-1.592	Destabilizing	1.0	D	0.883	deleterious	D	0.755415398	None	None	N
L/Q	0.9923	likely_pathogenic	0.9918	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/R	0.9913	likely_pathogenic	0.9908	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.755415398	None	None	N
L/S	0.9965	likely_pathogenic	0.9961	pathogenic	-3.502	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/T	0.98	likely_pathogenic	0.9773	pathogenic	-3.031	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/V	0.3005	likely_benign	0.2913	benign	-1.592	Destabilizing	0.999	D	0.572	neutral	D	0.628983435	None	None	N
L/W	0.9855	likely_pathogenic	0.9854	pathogenic	-2.22	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/Y	0.9802	likely_pathogenic	0.9791	pathogenic	-1.947	Destabilizing	1.0	D	0.865	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.