TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27518	82777;82778;82779	chr2:178563580;178563579;178563578	chr2:179428307;179428306;179428305
N2AB	25877	77854;77855;77856	chr2:178563580;178563579;178563578	chr2:179428307;179428306;179428305
N2A	24950	75073;75074;75075	chr2:178563580;178563579;178563578	chr2:179428307;179428306;179428305
N2B	18453	55582;55583;55584	chr2:178563580;178563579;178563578	chr2:179428307;179428306;179428305
Novex-1	18578	55957;55958;55959	chr2:178563580;178563579;178563578	chr2:179428307;179428306;179428305
Novex-2	18645	56158;56159;56160	chr2:178563580;178563579;178563578	chr2:179428307;179428306;179428305
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: Fn3-88
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.358
• 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	0.988	N	0.649	0.249	0.178374595973	gnomAD-4.0.0	1.36842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31868E-05	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	0.7602	likely_pathogenic	0.7833	pathogenic	-0.309	Destabilizing	0.968	D	0.571	neutral	None	None	None	None	N
K/C	0.889	likely_pathogenic	0.8996	pathogenic	-0.33	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/D	0.9791	likely_pathogenic	0.9775	pathogenic	-0.051	Destabilizing	0.995	D	0.759	deleterious	None	None	None	None	N
K/E	0.8357	likely_pathogenic	0.8477	pathogenic	0.001	Stabilizing	0.958	D	0.467	neutral	N	0.468393911	None	None	N
K/F	0.9654	likely_pathogenic	0.9697	pathogenic	-0.25	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/G	0.8883	likely_pathogenic	0.8926	pathogenic	-0.612	Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
K/H	0.6745	likely_pathogenic	0.6836	pathogenic	-1.03	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/I	0.7705	likely_pathogenic	0.7969	pathogenic	0.44	Stabilizing	0.995	D	0.757	deleterious	None	None	None	None	N
K/L	0.7247	likely_pathogenic	0.7583	pathogenic	0.44	Stabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
K/M	0.7176	likely_pathogenic	0.7432	pathogenic	0.395	Stabilizing	0.999	D	0.749	deleterious	N	0.472204932	None	None	N
K/N	0.9493	likely_pathogenic	0.9483	pathogenic	-0.119	Destabilizing	0.988	D	0.649	neutral	N	0.468544401	None	None	N
K/P	0.7703	likely_pathogenic	0.7824	pathogenic	0.221	Stabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
K/Q	0.4586	ambiguous	0.4876	ambiguous	-0.301	Destabilizing	0.988	D	0.623	neutral	N	0.484520944	None	None	N
K/R	0.0686	likely_benign	0.0726	benign	-0.403	Destabilizing	0.142	N	0.385	neutral	N	0.425531355	None	None	N
K/S	0.9054	likely_pathogenic	0.9091	pathogenic	-0.717	Destabilizing	0.968	D	0.563	neutral	None	None	None	None	N
K/T	0.7102	likely_pathogenic	0.7259	pathogenic	-0.486	Destabilizing	0.988	D	0.727	prob.delet.	N	0.481403281	None	None	N
K/V	0.6664	likely_pathogenic	0.7083	pathogenic	0.221	Stabilizing	0.995	D	0.745	deleterious	None	None	None	None	N
K/W	0.9414	likely_pathogenic	0.9506	pathogenic	-0.151	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/Y	0.9082	likely_pathogenic	0.9128	pathogenic	0.162	Stabilizing	0.998	D	0.749	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.