TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33631	101116;101117;101118	chr2:178535724;178535723;178535722	chr2:179400451;179400450;179400449
N2AB	31990	96193;96194;96195	chr2:178535724;178535723;178535722	chr2:179400451;179400450;179400449
N2A	31063	93412;93413;93414	chr2:178535724;178535723;178535722	chr2:179400451;179400450;179400449
N2B	24566	73921;73922;73923	chr2:178535724;178535723;178535722	chr2:179400451;179400450;179400449
Novex-1	24691	74296;74297;74298	chr2:178535724;178535723;178535722	chr2:179400451;179400450;179400449
Novex-2	24758	74497;74498;74499	chr2:178535724;178535723;178535722	chr2:179400451;179400450;179400449
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-159
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1128
• 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	1.0	N	0.716	0.489	0.15556083564	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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	0.9848	likely_pathogenic	0.9786	pathogenic	-1.006	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/C	0.98	likely_pathogenic	0.9779	pathogenic	-1.014	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
K/D	0.9951	likely_pathogenic	0.9913	pathogenic	-0.108	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/E	0.9672	likely_pathogenic	0.9442	pathogenic	0.056	Stabilizing	0.999	D	0.57	neutral	N	0.501141606	None	None	N
K/F	0.9933	likely_pathogenic	0.991	pathogenic	-0.698	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
K/G	0.9927	likely_pathogenic	0.9896	pathogenic	-1.395	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
K/H	0.8332	likely_pathogenic	0.8115	pathogenic	-1.609	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/I	0.9659	likely_pathogenic	0.9544	pathogenic	0.029	Stabilizing	0.999	D	0.856	deleterious	N	0.467780251	None	None	N
K/L	0.9538	likely_pathogenic	0.9487	pathogenic	0.029	Stabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
K/M	0.914	likely_pathogenic	0.8939	pathogenic	-0.126	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/N	0.979	likely_pathogenic	0.9694	pathogenic	-0.732	Destabilizing	1.0	D	0.716	prob.delet.	N	0.489367226	None	None	N
K/P	0.9986	likely_pathogenic	0.9985	pathogenic	-0.288	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/Q	0.779	likely_pathogenic	0.75	pathogenic	-0.694	Destabilizing	1.0	D	0.694	prob.neutral	N	0.500381137	None	None	N
K/R	0.1833	likely_benign	0.1827	benign	-0.626	Destabilizing	0.999	D	0.577	neutral	N	0.4779734	None	None	N
K/S	0.9892	likely_pathogenic	0.9845	pathogenic	-1.518	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
K/T	0.9647	likely_pathogenic	0.9506	pathogenic	-1.113	Destabilizing	1.0	D	0.794	deleterious	N	0.477757432	None	None	N
K/V	0.9522	likely_pathogenic	0.9414	pathogenic	-0.288	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
K/W	0.9884	likely_pathogenic	0.9862	pathogenic	-0.519	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
K/Y	0.9704	likely_pathogenic	0.9638	pathogenic	-0.232	Destabilizing	1.0	D	0.829	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.