TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27160	81703;81704;81705	chr2:178564654;178564653;178564652	chr2:179429381;179429380;179429379
N2AB	25519	76780;76781;76782	chr2:178564654;178564653;178564652	chr2:179429381;179429380;179429379
N2A	24592	73999;74000;74001	chr2:178564654;178564653;178564652	chr2:179429381;179429380;179429379
N2B	18095	54508;54509;54510	chr2:178564654;178564653;178564652	chr2:179429381;179429380;179429379
Novex-1	18220	54883;54884;54885	chr2:178564654;178564653;178564652	chr2:179429381;179429380;179429379
Novex-2	18287	55084;55085;55086	chr2:178564654;178564653;178564652	chr2:179429381;179429380;179429379
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: Fn3-85
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.5751
• Predicted PPI site: I

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	rs764904296	0.17	0.883	N	0.58	0.183	0.181679512989	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66113E-04
K/Q	rs749955874	0.203	0.062	N	0.405	0.147	0.141422826196	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
K/R	None	None	0.518	N	0.607	0.157	0.211220785272	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6905	likely_pathogenic	0.6476	pathogenic	0.006	Stabilizing	0.009	N	0.475	neutral	None	None	None	None	I
K/C	0.9084	likely_pathogenic	0.8979	pathogenic	-0.33	Destabilizing	0.987	D	0.761	deleterious	None	None	None	None	I
K/D	0.9022	likely_pathogenic	0.8821	pathogenic	0.063	Stabilizing	0.909	D	0.585	neutral	None	None	None	None	I
K/E	0.6153	likely_pathogenic	0.5457	ambiguous	0.058	Stabilizing	0.518	D	0.585	neutral	N	0.472874224	None	None	I
K/F	0.951	likely_pathogenic	0.9424	pathogenic	-0.285	Destabilizing	0.953	D	0.749	deleterious	None	None	None	None	I
K/G	0.806	likely_pathogenic	0.7795	pathogenic	-0.156	Destabilizing	0.587	D	0.563	neutral	None	None	None	None	I
K/H	0.5803	likely_pathogenic	0.5358	ambiguous	-0.351	Destabilizing	0.987	D	0.604	neutral	None	None	None	None	I
K/I	0.762	likely_pathogenic	0.7219	pathogenic	0.347	Stabilizing	0.883	D	0.747	deleterious	N	0.475377575	None	None	I
K/L	0.702	likely_pathogenic	0.6658	pathogenic	0.347	Stabilizing	0.587	D	0.581	neutral	None	None	None	None	I
K/M	0.6317	likely_pathogenic	0.582	pathogenic	0.116	Stabilizing	0.987	D	0.607	neutral	None	None	None	None	I
K/N	0.8372	likely_pathogenic	0.7888	pathogenic	0.159	Stabilizing	0.883	D	0.58	neutral	N	0.463310026	None	None	I
K/P	0.7992	likely_pathogenic	0.795	pathogenic	0.26	Stabilizing	0.953	D	0.599	neutral	None	None	None	None	I
K/Q	0.377	ambiguous	0.342	ambiguous	-0.009	Destabilizing	0.062	N	0.405	neutral	N	0.502853201	None	None	I
K/R	0.0945	likely_benign	0.0929	benign	-0.017	Destabilizing	0.518	D	0.607	neutral	N	0.470242138	None	None	I
K/S	0.8242	likely_pathogenic	0.7856	pathogenic	-0.317	Destabilizing	0.587	D	0.536	neutral	None	None	None	None	I
K/T	0.6153	likely_pathogenic	0.5634	ambiguous	-0.183	Destabilizing	0.682	D	0.597	neutral	N	0.513627556	None	None	I
K/V	0.6847	likely_pathogenic	0.6415	pathogenic	0.26	Stabilizing	0.833	D	0.565	neutral	None	None	None	None	I
K/W	0.9284	likely_pathogenic	0.9229	pathogenic	-0.323	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	I
K/Y	0.8743	likely_pathogenic	0.8608	pathogenic	0.041	Stabilizing	0.984	D	0.734	deleterious	None	None	None	None	I

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.