TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8687	26284;26285;26286	chr2:178715127;178715126;178715125	chr2:179579854;179579853;179579852
N2AB	8370	25333;25334;25335	chr2:178715127;178715126;178715125	chr2:179579854;179579853;179579852
N2A	7443	22552;22553;22554	chr2:178715127;178715126;178715125	chr2:179579854;179579853;179579852
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-72
• Domain position: 45
• Structural Position: 102
• Q(SASA): 1.0205
• 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	0.424	N	0.439	0.068	0.107399877778	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/Q	rs753822494	-0.05	0.082	N	0.427	0.08	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
K/Q	rs753822494	-0.05	0.082	N	0.427	0.08	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs753822494	-0.05	0.082	N	0.427	0.08	None	gnomAD-4.0.0	4.05977E-06	None	None	None	None	N	None	5.24182E-05	0	None	0	0	None	0	0	1.20492E-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	0.862	likely_pathogenic	0.807	pathogenic	-0.153	Destabilizing	0.494	N	0.443	neutral	None	None	None	None	N
K/C	0.9544	likely_pathogenic	0.9343	pathogenic	-0.733	Destabilizing	0.988	D	0.494	neutral	None	None	None	None	N
K/D	0.8978	likely_pathogenic	0.8696	pathogenic	-0.423	Destabilizing	0.003	N	0.305	neutral	None	None	None	None	N
K/E	0.6932	likely_pathogenic	0.6307	pathogenic	-0.446	Destabilizing	0.044	N	0.441	neutral	N	0.480429341	None	None	N
K/F	0.9722	likely_pathogenic	0.9582	pathogenic	-0.568	Destabilizing	0.734	D	0.464	neutral	None	None	None	None	N
K/G	0.8141	likely_pathogenic	0.7616	pathogenic	-0.228	Destabilizing	0.494	N	0.452	neutral	None	None	None	None	N
K/H	0.6975	likely_pathogenic	0.6348	pathogenic	-0.256	Destabilizing	0.742	D	0.449	neutral	None	None	None	None	N
K/I	0.8386	likely_pathogenic	0.7902	pathogenic	-0.035	Destabilizing	0.17	N	0.467	neutral	None	None	None	None	N
K/L	0.8063	likely_pathogenic	0.7627	pathogenic	-0.035	Destabilizing	0.028	N	0.435	neutral	None	None	None	None	N
K/M	0.7221	likely_pathogenic	0.667	pathogenic	-0.364	Destabilizing	0.878	D	0.453	neutral	N	0.458667855	None	None	N
K/N	0.8401	likely_pathogenic	0.8123	pathogenic	-0.306	Destabilizing	0.424	N	0.439	neutral	N	0.491782485	None	None	N
K/P	0.8504	likely_pathogenic	0.7892	pathogenic	-0.056	Destabilizing	0.874	D	0.441	neutral	None	None	None	None	N
K/Q	0.4091	ambiguous	0.349	ambiguous	-0.412	Destabilizing	0.082	N	0.427	neutral	N	0.491051766	None	None	N
K/R	0.0937	likely_benign	0.0845	benign	-0.331	Destabilizing	None	N	0.217	neutral	N	0.412225623	None	None	N
K/S	0.8563	likely_pathogenic	0.8144	pathogenic	-0.635	Destabilizing	0.494	N	0.429	neutral	None	None	None	None	N
K/T	0.7223	likely_pathogenic	0.6694	pathogenic	-0.563	Destabilizing	0.181	N	0.445	neutral	N	0.459536781	None	None	N
K/V	0.823	likely_pathogenic	0.7775	pathogenic	-0.056	Destabilizing	0.117	N	0.429	neutral	None	None	None	None	N
K/W	0.9199	likely_pathogenic	0.8859	pathogenic	-0.694	Destabilizing	0.992	D	0.541	neutral	None	None	None	None	N
K/Y	0.9049	likely_pathogenic	0.871	pathogenic	-0.368	Destabilizing	0.245	N	0.453	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.