TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27917	83974;83975;83976	chr2:178562383;178562382;178562381	chr2:179427110;179427109;179427108
N2AB	26276	79051;79052;79053	chr2:178562383;178562382;178562381	chr2:179427110;179427109;179427108
N2A	25349	76270;76271;76272	chr2:178562383;178562382;178562381	chr2:179427110;179427109;179427108
N2B	18852	56779;56780;56781	chr2:178562383;178562382;178562381	chr2:179427110;179427109;179427108
Novex-1	18977	57154;57155;57156	chr2:178562383;178562382;178562381	chr2:179427110;179427109;179427108
Novex-2	19044	57355;57356;57357	chr2:178562383;178562382;178562381	chr2:179427110;179427109;179427108
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: Fn3-91
• Domain position: 55
• Structural Position: 83
• Q(SASA): 0.9002
• 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/E	rs1363288051	0.085	0.777	N	0.563	0.218	0.250579442822	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.35E-05	None	0	0	0
K/E	rs1363288051	0.085	0.777	N	0.563	0.218	0.250579442822	gnomAD-4.0.0	2.05588E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80019E-06	1.16724E-05	0
K/N	rs746705899	None	0.976	N	0.675	0.251	0.194818534648	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs746705899	None	0.976	N	0.675	0.251	0.194818534648	gnomAD-4.0.0	1.24129E-06	None	None	None	None	N	None	1.33704E-05	0	None	0	0	None	0	0	8.48215E-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	0.7634	likely_pathogenic	0.8222	pathogenic	0.022	Stabilizing	0.885	D	0.537	neutral	None	None	None	None	N
K/C	0.8974	likely_pathogenic	0.9246	pathogenic	-0.372	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
K/D	0.8782	likely_pathogenic	0.9102	pathogenic	0.105	Stabilizing	0.982	D	0.632	neutral	None	None	None	None	N
K/E	0.6794	likely_pathogenic	0.7475	pathogenic	0.111	Stabilizing	0.777	D	0.563	neutral	N	0.521847181	None	None	N
K/F	0.9571	likely_pathogenic	0.9741	pathogenic	-0.212	Destabilizing	0.977	D	0.729	prob.delet.	None	None	None	None	N
K/G	0.7573	likely_pathogenic	0.8121	pathogenic	-0.158	Destabilizing	0.885	D	0.556	neutral	None	None	None	None	N
K/H	0.5415	ambiguous	0.624	pathogenic	-0.346	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
K/I	0.8368	likely_pathogenic	0.8905	pathogenic	0.412	Stabilizing	0.762	D	0.736	prob.delet.	None	None	None	None	N
K/L	0.7576	likely_pathogenic	0.8251	pathogenic	0.412	Stabilizing	0.613	D	0.561	neutral	None	None	None	None	N
K/M	0.6552	likely_pathogenic	0.7324	pathogenic	0.103	Stabilizing	0.991	D	0.696	prob.neutral	N	0.498831563	None	None	N
K/N	0.7704	likely_pathogenic	0.8242	pathogenic	0.095	Stabilizing	0.976	D	0.675	prob.neutral	N	0.487099889	None	None	N
K/P	0.837	likely_pathogenic	0.8589	pathogenic	0.309	Stabilizing	0.991	D	0.721	prob.delet.	None	None	None	None	N
K/Q	0.3469	ambiguous	0.4063	ambiguous	-0.047	Destabilizing	0.831	D	0.711	prob.delet.	N	0.474282074	None	None	N
K/R	0.0929	likely_benign	0.1034	benign	-0.065	Destabilizing	0.682	D	0.591	neutral	N	0.511398114	None	None	N
K/S	0.78	likely_pathogenic	0.8341	pathogenic	-0.379	Destabilizing	0.171	N	0.34	neutral	None	None	None	None	N
K/T	0.5601	ambiguous	0.6543	pathogenic	-0.229	Destabilizing	0.635	D	0.615	neutral	D	0.522868688	None	None	N
K/V	0.7947	likely_pathogenic	0.8568	pathogenic	0.309	Stabilizing	0.676	D	0.643	neutral	None	None	None	None	N
K/W	0.9101	likely_pathogenic	0.9382	pathogenic	-0.251	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
K/Y	0.879	likely_pathogenic	0.9165	pathogenic	0.109	Stabilizing	0.939	D	0.709	prob.delet.	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.