TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14018	42277;42278;42279	chr2:178634822;178634821;178634820	chr2:179499549;179499548;179499547
N2AB	12377	37354;37355;37356	chr2:178634822;178634821;178634820	chr2:179499549;179499548;179499547
N2A	11450	34573;34574;34575	chr2:178634822;178634821;178634820	chr2:179499549;179499548;179499547
N2B	4953	15082;15083;15084	chr2:178634822;178634821;178634820	chr2:179499549;179499548;179499547
Novex-1	5078	15457;15458;15459	chr2:178634822;178634821;178634820	chr2:179499549;179499548;179499547
Novex-2	5145	15658;15659;15660	chr2:178634822;178634821;178634820	chr2:179499549;179499548;179499547
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-90
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.5543
• 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	rs766572300	0.056	0.999	N	0.741	0.173	0.146414634003	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66778E-04
K/N	rs766572300	0.056	0.999	N	0.741	0.173	0.146414634003	gnomAD-4.0.0	2.05553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80002E-06	0	1.65881E-05

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	0.8492	likely_pathogenic	0.8112	pathogenic	-0.747	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
K/C	0.893	likely_pathogenic	0.8714	pathogenic	-0.802	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/D	0.9372	likely_pathogenic	0.9283	pathogenic	-0.343	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
K/E	0.5777	likely_pathogenic	0.5352	ambiguous	-0.213	Destabilizing	0.997	D	0.791	deleterious	N	0.497593633	None	None	N
K/F	0.9598	likely_pathogenic	0.9428	pathogenic	-0.385	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/G	0.906	likely_pathogenic	0.8703	pathogenic	-1.135	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
K/H	0.522	ambiguous	0.4945	ambiguous	-1.473	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/I	0.6705	likely_pathogenic	0.6204	pathogenic	0.27	Stabilizing	0.999	D	0.779	deleterious	N	0.455606064	None	None	N
K/L	0.7273	likely_pathogenic	0.6579	pathogenic	0.27	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
K/M	0.5801	likely_pathogenic	0.5278	ambiguous	0.156	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/N	0.7776	likely_pathogenic	0.7528	pathogenic	-0.666	Destabilizing	0.999	D	0.741	deleterious	N	0.459300163	None	None	N
K/P	0.991	likely_pathogenic	0.9856	pathogenic	-0.039	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
K/Q	0.2837	likely_benign	0.2623	benign	-0.728	Destabilizing	0.999	D	0.726	deleterious	N	0.458706062	None	None	N
K/R	0.116	likely_benign	0.1125	benign	-0.71	Destabilizing	0.997	D	0.713	prob.delet.	N	0.429251761	None	None	N
K/S	0.8477	likely_pathogenic	0.8075	pathogenic	-1.347	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
K/T	0.5635	ambiguous	0.5102	ambiguous	-1.0	Destabilizing	0.999	D	0.815	deleterious	N	0.426989824	None	None	N
K/V	0.6353	likely_pathogenic	0.5929	pathogenic	-0.039	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
K/W	0.9608	likely_pathogenic	0.9414	pathogenic	-0.24	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Y	0.9043	likely_pathogenic	0.8733	pathogenic	0.058	Stabilizing	1.0	D	0.775	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.