TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24751	74476;74477;74478	chr2:178571881;178571880;178571879	chr2:179436608;179436607;179436606
N2AB	23110	69553;69554;69555	chr2:178571881;178571880;178571879	chr2:179436608;179436607;179436606
N2A	22183	66772;66773;66774	chr2:178571881;178571880;178571879	chr2:179436608;179436607;179436606
N2B	15686	47281;47282;47283	chr2:178571881;178571880;178571879	chr2:179436608;179436607;179436606
Novex-1	15811	47656;47657;47658	chr2:178571881;178571880;178571879	chr2:179436608;179436607;179436606
Novex-2	15878	47857;47858;47859	chr2:178571881;178571880;178571879	chr2:179436608;179436607;179436606
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-133
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2829
• 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/R	rs1280335155	-0.523	0.999	N	0.583	0.386	0.223847106136	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs1280335155	-0.523	0.999	N	0.583	0.386	0.223847106136	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85951E-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	0.9506	likely_pathogenic	0.9523	pathogenic	-0.944	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
K/C	0.9262	likely_pathogenic	0.9228	pathogenic	-1.066	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
K/D	0.9919	likely_pathogenic	0.9925	pathogenic	-0.608	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/E	0.886	likely_pathogenic	0.8903	pathogenic	-0.442	Destabilizing	0.999	D	0.59	neutral	D	0.529779245	None	None	N
K/F	0.9684	likely_pathogenic	0.97	pathogenic	-0.613	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
K/G	0.9737	likely_pathogenic	0.9751	pathogenic	-1.347	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/H	0.6943	likely_pathogenic	0.6834	pathogenic	-1.717	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/I	0.848	likely_pathogenic	0.8659	pathogenic	0.131	Stabilizing	1.0	D	0.869	deleterious	N	0.517155492	None	None	N
K/L	0.8372	likely_pathogenic	0.8506	pathogenic	0.131	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/M	0.7368	likely_pathogenic	0.7521	pathogenic	0.008	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/N	0.9695	likely_pathogenic	0.9698	pathogenic	-0.906	Destabilizing	1.0	D	0.716	prob.delet.	D	0.52294239	None	None	N
K/P	0.997	likely_pathogenic	0.9977	pathogenic	-0.199	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/Q	0.5462	ambiguous	0.5541	ambiguous	-0.907	Destabilizing	1.0	D	0.691	prob.neutral	D	0.522435411	None	None	N
K/R	0.1029	likely_benign	0.1051	benign	-0.811	Destabilizing	0.999	D	0.583	neutral	N	0.459280647	None	None	N
K/S	0.9682	likely_pathogenic	0.9683	pathogenic	-1.598	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/T	0.8638	likely_pathogenic	0.8833	pathogenic	-1.205	Destabilizing	1.0	D	0.774	deleterious	D	0.522688901	None	None	N
K/V	0.8398	likely_pathogenic	0.8522	pathogenic	-0.199	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
K/W	0.9524	likely_pathogenic	0.9561	pathogenic	-0.509	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
K/Y	0.9168	likely_pathogenic	0.916	pathogenic	-0.159	Destabilizing	1.0	D	0.848	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.