TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4923	14992;14993;14994	chr2:178735679;178735678;178735677	chr2:179600406;179600405;179600404
N2AB	4606	14041;14042;14043	chr2:178735679;178735678;178735677	chr2:179600406;179600405;179600404
N2A	3679	11260;11261;11262	chr2:178735679;178735678;178735677	chr2:179600406;179600405;179600404
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-32
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1776
• 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
K/N	None	None	0.997	D	0.647	0.343	0.226586394389	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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
K/A	0.7965	likely_pathogenic	0.8896	pathogenic	-1.13	Destabilizing	0.983	D	0.511	neutral	None	None	None	None	N
K/C	0.8089	likely_pathogenic	0.88	pathogenic	-1.376	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/D	0.9664	likely_pathogenic	0.9798	pathogenic	-0.785	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
K/E	0.5944	likely_pathogenic	0.7261	pathogenic	-0.635	Destabilizing	0.978	D	0.447	neutral	D	0.735571438	None	None	N
K/F	0.8897	likely_pathogenic	0.9399	pathogenic	-1.058	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
K/G	0.8764	likely_pathogenic	0.9323	pathogenic	-1.5	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/H	0.4557	ambiguous	0.5442	ambiguous	-1.92	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
K/I	0.6569	likely_pathogenic	0.7798	pathogenic	-0.149	Destabilizing	0.999	D	0.835	deleterious	D	0.627555094	None	None	N
K/L	0.6569	likely_pathogenic	0.7789	pathogenic	-0.149	Destabilizing	0.995	D	0.707	prob.neutral	None	None	None	None	N
K/M	0.4841	ambiguous	0.6185	pathogenic	-0.139	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/N	0.8708	likely_pathogenic	0.9175	pathogenic	-1.031	Destabilizing	0.997	D	0.647	neutral	D	0.639010668	None	None	N
K/P	0.986	likely_pathogenic	0.9921	pathogenic	-0.449	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
K/Q	0.3026	likely_benign	0.4199	ambiguous	-1.106	Destabilizing	0.994	D	0.634	neutral	D	0.582239439	None	None	N
K/R	0.0749	likely_benign	0.0835	benign	-0.829	Destabilizing	0.121	N	0.246	neutral	N	0.464175359	None	None	N
K/S	0.8673	likely_pathogenic	0.9268	pathogenic	-1.766	Destabilizing	0.992	D	0.523	neutral	None	None	None	None	N
K/T	0.7175	likely_pathogenic	0.8278	pathogenic	-1.388	Destabilizing	0.997	D	0.708	prob.delet.	D	0.648335331	None	None	N
K/V	0.6114	likely_pathogenic	0.741	pathogenic	-0.449	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
K/W	0.8507	likely_pathogenic	0.9084	pathogenic	-0.911	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
K/Y	0.7886	likely_pathogenic	0.8568	pathogenic	-0.546	Destabilizing	0.999	D	0.822	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.