TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8678	26257;26258;26259	chr2:178715154;178715153;178715152	chr2:179579881;179579880;179579879
N2AB	8361	25306;25307;25308	chr2:178715154;178715153;178715152	chr2:179579881;179579880;179579879
N2A	7434	22525;22526;22527	chr2:178715154;178715153;178715152	chr2:179579881;179579880;179579879
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-72
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1359
• 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/E	rs2077288683	None	1.0	D	0.525	0.544	0.489036454283	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs2077288683	None	1.0	D	0.525	0.544	0.489036454283	gnomAD-4.0.0	2.5623E-06	None	None	None	None	N	None	1.69113E-05	0	None	0	0	None	0	0	2.39339E-06	0	0
K/T	rs1208054129	None	1.0	N	0.782	0.63	0.4897983601	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs1208054129	None	1.0	N	0.782	0.63	0.4897983601	gnomAD-4.0.0	5.12478E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.57355E-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	0.9698	likely_pathogenic	0.9778	pathogenic	-1.026	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/C	0.964	likely_pathogenic	0.9731	pathogenic	-0.987	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
K/D	0.9948	likely_pathogenic	0.9962	pathogenic	-0.548	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/E	0.9302	likely_pathogenic	0.9495	pathogenic	-0.355	Destabilizing	1.0	D	0.525	neutral	D	0.541300135	None	None	N
K/F	0.9802	likely_pathogenic	0.987	pathogenic	-0.489	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
K/G	0.9799	likely_pathogenic	0.986	pathogenic	-1.473	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/H	0.7569	likely_pathogenic	0.7888	pathogenic	-1.756	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
K/I	0.8983	likely_pathogenic	0.9273	pathogenic	0.182	Stabilizing	0.999	D	0.887	deleterious	N	0.503824177	None	None	N
K/L	0.8676	likely_pathogenic	0.9004	pathogenic	0.182	Stabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
K/M	0.8127	likely_pathogenic	0.8588	pathogenic	0.048	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/N	0.9772	likely_pathogenic	0.9847	pathogenic	-1.011	Destabilizing	1.0	D	0.682	prob.neutral	D	0.52969034	None	None	N
K/P	0.9971	likely_pathogenic	0.998	pathogenic	-0.193	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
K/Q	0.6464	likely_pathogenic	0.7014	pathogenic	-0.911	Destabilizing	1.0	D	0.68	prob.neutral	N	0.50844576	None	None	N
K/R	0.1076	likely_benign	0.111	benign	-0.936	Destabilizing	0.999	D	0.56	neutral	N	0.516761074	None	None	N
K/S	0.9815	likely_pathogenic	0.9861	pathogenic	-1.718	Destabilizing	1.0	D	0.519	neutral	None	None	None	None	N
K/T	0.9431	likely_pathogenic	0.9571	pathogenic	-1.278	Destabilizing	1.0	D	0.782	deleterious	N	0.517915961	None	None	N
K/V	0.8776	likely_pathogenic	0.907	pathogenic	-0.193	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
K/W	0.9645	likely_pathogenic	0.9726	pathogenic	-0.37	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/Y	0.9463	likely_pathogenic	0.9576	pathogenic	-0.079	Destabilizing	1.0	D	0.877	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.