TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17839	53740;53741;53742	chr2:178607087;178607086;178607085	chr2:179471814;179471813;179471812
N2AB	16198	48817;48818;48819	chr2:178607087;178607086;178607085	chr2:179471814;179471813;179471812
N2A	15271	46036;46037;46038	chr2:178607087;178607086;178607085	chr2:179471814;179471813;179471812
N2B	8774	26545;26546;26547	chr2:178607087;178607086;178607085	chr2:179471814;179471813;179471812
Novex-1	8899	26920;26921;26922	chr2:178607087;178607086;178607085	chr2:179471814;179471813;179471812
Novex-2	8966	27121;27122;27123	chr2:178607087;178607086;178607085	chr2:179471814;179471813;179471812
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-17
• Domain position: 76
• Structural Position: 110
• Q(SASA): 0.0844
• 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
A/V	None	None	0.977	D	0.671	0.66	0.590373781641	gnomAD-4.0.0	1.59479E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02939E-05

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
A/C	0.8709	likely_pathogenic	0.858	pathogenic	-1.705	Destabilizing	0.483	N	0.459	neutral	None	None	None	None	N
A/D	0.9992	likely_pathogenic	0.9989	pathogenic	-2.955	Highly Destabilizing	0.999	D	0.913	deleterious	D	0.552317041	None	None	N
A/E	0.9981	likely_pathogenic	0.997	pathogenic	-2.72	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
A/F	0.994	likely_pathogenic	0.9918	pathogenic	-0.784	Destabilizing	0.999	D	0.938	deleterious	None	None	None	None	N
A/G	0.4296	ambiguous	0.4484	ambiguous	-2.137	Highly Destabilizing	0.989	D	0.639	neutral	D	0.528172398	None	None	N
A/H	0.9985	likely_pathogenic	0.9983	pathogenic	-2.213	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
A/I	0.9911	likely_pathogenic	0.9802	pathogenic	-0.39	Destabilizing	0.995	D	0.859	deleterious	None	None	None	None	N
A/K	0.9995	likely_pathogenic	0.9991	pathogenic	-1.471	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
A/L	0.9517	likely_pathogenic	0.9221	pathogenic	-0.39	Destabilizing	0.966	D	0.778	deleterious	None	None	None	None	N
A/M	0.9871	likely_pathogenic	0.9809	pathogenic	-0.895	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
A/N	0.9972	likely_pathogenic	0.9958	pathogenic	-1.926	Destabilizing	0.999	D	0.924	deleterious	None	None	None	None	N
A/P	0.8398	likely_pathogenic	0.8635	pathogenic	-0.783	Destabilizing	0.999	D	0.858	deleterious	D	0.52960443	None	None	N
A/Q	0.9936	likely_pathogenic	0.9915	pathogenic	-1.663	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
A/R	0.9957	likely_pathogenic	0.9937	pathogenic	-1.552	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
A/S	0.5573	ambiguous	0.5296	ambiguous	-2.294	Highly Destabilizing	0.977	D	0.639	neutral	N	0.498823515	None	None	N
A/T	0.9417	likely_pathogenic	0.9	pathogenic	-1.945	Destabilizing	0.993	D	0.759	deleterious	D	0.536904903	None	None	N
A/V	0.9531	likely_pathogenic	0.904	pathogenic	-0.783	Destabilizing	0.977	D	0.671	neutral	D	0.538679329	None	None	N
A/W	0.9994	likely_pathogenic	0.9992	pathogenic	-1.487	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
A/Y	0.9981	likely_pathogenic	0.9973	pathogenic	-1.102	Destabilizing	1.0	D	0.941	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.