TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8773	26542;26543;26544	chr2:178714457;178714456;178714455	chr2:179579184;179579183;179579182
N2AB	8456	25591;25592;25593	chr2:178714457;178714456;178714455	chr2:179579184;179579183;179579182
N2A	7529	22810;22811;22812	chr2:178714457;178714456;178714455	chr2:179579184;179579183;179579182
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-73
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.7553
• 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	0.007	N	0.277	0.031	0.0401082797425	gnomAD-4.0.0	3.42147E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49769E-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	0.2801	likely_benign	0.375	ambiguous	0.112	Stabilizing	0.256	N	0.468	neutral	None	None	None	None	N
K/C	0.7301	likely_pathogenic	0.8196	pathogenic	-0.197	Destabilizing	0.982	D	0.556	neutral	None	None	None	None	N
K/D	0.3924	ambiguous	0.4978	ambiguous	-0.008	Destabilizing	0.256	N	0.452	neutral	None	None	None	None	N
K/E	0.1487	likely_benign	0.2163	benign	-0.015	Destabilizing	0.072	N	0.452	neutral	N	0.490550334	None	None	N
K/F	0.7355	likely_pathogenic	0.8361	pathogenic	-0.185	Destabilizing	0.66	D	0.529	neutral	None	None	None	None	N
K/G	0.3108	likely_benign	0.4008	ambiguous	-0.042	Destabilizing	0.407	N	0.474	neutral	None	None	None	None	N
K/H	0.3104	likely_benign	0.3649	ambiguous	-0.215	Destabilizing	0.669	D	0.453	neutral	None	None	None	None	N
K/I	0.3865	ambiguous	0.5222	ambiguous	0.434	Stabilizing	0.126	N	0.519	neutral	None	None	None	None	N
K/L	0.3996	ambiguous	0.5167	ambiguous	0.434	Stabilizing	0.02	N	0.445	neutral	None	None	None	None	N
K/M	0.2583	likely_benign	0.3609	ambiguous	0.132	Stabilizing	0.835	D	0.461	neutral	N	0.485659654	None	None	N
K/N	0.3031	likely_benign	0.4061	ambiguous	0.313	Stabilizing	0.007	N	0.277	neutral	N	0.419900957	None	None	N
K/P	0.6405	likely_pathogenic	0.6981	pathogenic	0.353	Stabilizing	0.83	D	0.445	neutral	None	None	None	None	N
K/Q	0.1372	likely_benign	0.1743	benign	0.152	Stabilizing	0.18	N	0.423	neutral	N	0.455020551	None	None	N
K/R	0.0802	likely_benign	0.0821	benign	0.08	Stabilizing	0.001	N	0.265	neutral	N	0.472871316	None	None	N
K/S	0.3131	likely_benign	0.4008	ambiguous	-0.111	Destabilizing	0.026	N	0.288	neutral	None	None	None	None	N
K/T	0.1778	likely_benign	0.2384	benign	0.012	Stabilizing	0.135	N	0.481	neutral	N	0.483952436	None	None	N
K/V	0.361	ambiguous	0.4803	ambiguous	0.353	Stabilizing	0.085	N	0.468	neutral	None	None	None	None	N
K/W	0.7328	likely_pathogenic	0.8079	pathogenic	-0.259	Destabilizing	0.988	D	0.614	neutral	None	None	None	None	N
K/Y	0.5882	likely_pathogenic	0.7035	pathogenic	0.108	Stabilizing	0.185	N	0.507	neutral	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.