TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13878	41857;41858;41859	chr2:178635692;178635691;178635690	chr2:179500419;179500418;179500417
N2AB	12237	36934;36935;36936	chr2:178635692;178635691;178635690	chr2:179500419;179500418;179500417
N2A	11310	34153;34154;34155	chr2:178635692;178635691;178635690	chr2:179500419;179500418;179500417
N2B	4813	14662;14663;14664	chr2:178635692;178635691;178635690	chr2:179500419;179500418;179500417
Novex-1	4938	15037;15038;15039	chr2:178635692;178635691;178635690	chr2:179500419;179500418;179500417
Novex-2	5005	15238;15239;15240	chr2:178635692;178635691;178635690	chr2:179500419;179500418;179500417
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-89
• Domain position: 3
• Structural Position: 5
• Q(SASA): 0.344
• 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	0.999	D	0.66	0.232	0.17258766438	gnomAD-4.0.0	6.89888E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04254E-07	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	0.8016	likely_pathogenic	0.92	pathogenic	0.008	Stabilizing	0.997	D	0.577	neutral	None	None	None	None	N
K/C	0.9058	likely_pathogenic	0.9552	pathogenic	-0.283	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/D	0.9343	likely_pathogenic	0.9725	pathogenic	0.126	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
K/E	0.6221	likely_pathogenic	0.8281	pathogenic	0.156	Stabilizing	0.991	D	0.536	neutral	D	0.548257807	None	None	N
K/F	0.9532	likely_pathogenic	0.9772	pathogenic	-0.066	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/G	0.8673	likely_pathogenic	0.9403	pathogenic	-0.221	Destabilizing	0.999	D	0.67	prob.neutral	None	None	None	None	N
K/H	0.4875	ambiguous	0.6552	pathogenic	-0.422	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/I	0.8206	likely_pathogenic	0.8919	pathogenic	0.542	Stabilizing	1.0	D	0.831	deleterious	D	0.546466703	None	None	N
K/L	0.7498	likely_pathogenic	0.8516	pathogenic	0.542	Stabilizing	0.999	D	0.67	prob.neutral	None	None	None	None	N
K/M	0.6612	likely_pathogenic	0.7972	pathogenic	0.167	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/N	0.8079	likely_pathogenic	0.9021	pathogenic	0.137	Stabilizing	0.999	D	0.66	prob.neutral	D	0.553537344	None	None	N
K/P	0.9782	likely_pathogenic	0.9897	pathogenic	0.393	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Q	0.3269	likely_benign	0.5211	ambiguous	0.017	Stabilizing	0.997	D	0.663	prob.neutral	D	0.544375937	None	None	N
K/R	0.1211	likely_benign	0.1598	benign	-0.088	Destabilizing	0.451	N	0.333	neutral	N	0.508182075	None	None	N
K/S	0.8221	likely_pathogenic	0.9184	pathogenic	-0.354	Destabilizing	0.997	D	0.618	neutral	None	None	None	None	N
K/T	0.5775	likely_pathogenic	0.7609	pathogenic	-0.165	Destabilizing	0.999	D	0.715	prob.delet.	D	0.544560643	None	None	N
K/V	0.7689	likely_pathogenic	0.8639	pathogenic	0.393	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
K/W	0.9443	likely_pathogenic	0.9714	pathogenic	-0.079	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Y	0.8873	likely_pathogenic	0.9395	pathogenic	0.26	Stabilizing	1.0	D	0.808	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.