TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15414	46465;46466;46467	chr2:178620281;178620280;178620279	chr2:179485008;179485007;179485006
N2AB	13773	41542;41543;41544	chr2:178620281;178620280;178620279	chr2:179485008;179485007;179485006
N2A	12846	38761;38762;38763	chr2:178620281;178620280;178620279	chr2:179485008;179485007;179485006
N2B	6349	19270;19271;19272	chr2:178620281;178620280;178620279	chr2:179485008;179485007;179485006
Novex-1	6474	19645;19646;19647	chr2:178620281;178620280;178620279	chr2:179485008;179485007;179485006
Novex-2	6541	19846;19847;19848	chr2:178620281;178620280;178620279	chr2:179485008;179485007;179485006
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-106
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1072
• 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
L/P	None	None	1.0	D	0.825	0.776	0.890016908248	gnomAD-4.0.0	7.16396E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.24618E-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
L/A	0.9206	likely_pathogenic	0.9527	pathogenic	-2.75	Highly Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
L/C	0.921	likely_pathogenic	0.9524	pathogenic	-2.331	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/D	0.998	likely_pathogenic	0.9991	pathogenic	-3.381	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/E	0.9891	likely_pathogenic	0.9943	pathogenic	-3.196	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/F	0.6565	likely_pathogenic	0.815	pathogenic	-1.583	Destabilizing	1.0	D	0.81	deleterious	D	0.564039147	None	None	N
L/G	0.9843	likely_pathogenic	0.9913	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
L/H	0.9745	likely_pathogenic	0.9878	pathogenic	-2.54	Highly Destabilizing	1.0	D	0.812	deleterious	D	0.69256767	None	None	N
L/I	0.2034	likely_benign	0.2371	benign	-1.321	Destabilizing	0.999	D	0.529	neutral	N	0.498738171	None	None	N
L/K	0.9801	likely_pathogenic	0.9868	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/M	0.3891	ambiguous	0.4939	ambiguous	-1.438	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/N	0.9854	likely_pathogenic	0.9923	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/P	0.9819	likely_pathogenic	0.993	pathogenic	-1.78	Destabilizing	1.0	D	0.825	deleterious	D	0.632229108	None	None	N
L/Q	0.9659	likely_pathogenic	0.9834	pathogenic	-2.366	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/R	0.9698	likely_pathogenic	0.981	pathogenic	-1.696	Destabilizing	1.0	D	0.82	deleterious	D	0.69256767	None	None	N
L/S	0.9833	likely_pathogenic	0.9915	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/T	0.8932	likely_pathogenic	0.9141	pathogenic	-2.749	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/V	0.196	likely_benign	0.2386	benign	-1.78	Destabilizing	0.999	D	0.521	neutral	N	0.464368839	None	None	N
L/W	0.9681	likely_pathogenic	0.987	pathogenic	-1.94	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/Y	0.9586	likely_pathogenic	0.9832	pathogenic	-1.756	Destabilizing	1.0	D	0.835	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.