TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27981	84166;84167;84168	chr2:178562191;178562190;178562189	chr2:179426918;179426917;179426916
N2AB	26340	79243;79244;79245	chr2:178562191;178562190;178562189	chr2:179426918;179426917;179426916
N2A	25413	76462;76463;76464	chr2:178562191;178562190;178562189	chr2:179426918;179426917;179426916
N2B	18916	56971;56972;56973	chr2:178562191;178562190;178562189	chr2:179426918;179426917;179426916
Novex-1	19041	57346;57347;57348	chr2:178562191;178562190;178562189	chr2:179426918;179426917;179426916
Novex-2	19108	57547;57548;57549	chr2:178562191;178562190;178562189	chr2:179426918;179426917;179426916
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: Ig-142
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.7308
• 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/Q	rs1472389863	0.403	0.82	N	0.593	0.182	0.176091768786	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/Q	rs1472389863	0.403	0.82	N	0.593	0.182	0.176091768786	gnomAD-4.0.0	1.59331E-06	None	None	None	None	N	None	0	2.29211E-05	None	0	0	None	0	0	0	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	0.4075	ambiguous	0.4486	ambiguous	-0.3	Destabilizing	0.633	D	0.577	neutral	None	None	None	None	N
K/C	0.5889	likely_pathogenic	0.6059	pathogenic	-0.408	Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	N
K/D	0.6922	likely_pathogenic	0.7091	pathogenic	0.235	Stabilizing	0.633	D	0.589	neutral	None	None	None	None	N
K/E	0.2725	likely_benign	0.3032	benign	0.28	Stabilizing	0.008	N	0.383	neutral	N	0.509386811	None	None	N
K/F	0.7457	likely_pathogenic	0.766	pathogenic	-0.368	Destabilizing	0.923	D	0.699	prob.neutral	None	None	None	None	N
K/G	0.6236	likely_pathogenic	0.6574	pathogenic	-0.57	Destabilizing	0.923	D	0.585	neutral	None	None	None	None	N
K/H	0.2334	likely_benign	0.2262	benign	-0.961	Destabilizing	0.989	D	0.659	neutral	None	None	None	None	N
K/I	0.2926	likely_benign	0.3208	benign	0.35	Stabilizing	0.858	D	0.701	prob.neutral	None	None	None	None	N
K/L	0.3546	ambiguous	0.3969	ambiguous	0.35	Stabilizing	0.372	N	0.561	neutral	None	None	None	None	N
K/M	0.2063	likely_benign	0.24	benign	0.285	Stabilizing	0.156	N	0.492	neutral	N	0.493635371	None	None	N
K/N	0.4409	ambiguous	0.4753	ambiguous	0.029	Stabilizing	0.901	D	0.602	neutral	N	0.470388492	None	None	N
K/P	0.9046	likely_pathogenic	0.9339	pathogenic	0.164	Stabilizing	0.961	D	0.681	prob.neutral	None	None	None	None	N
K/Q	0.128	likely_benign	0.1349	benign	-0.158	Destabilizing	0.82	D	0.593	neutral	N	0.510253603	None	None	N
K/R	0.082	likely_benign	0.0819	benign	-0.218	Destabilizing	0.722	D	0.544	neutral	N	0.485509874	None	None	N
K/S	0.4316	ambiguous	0.465	ambiguous	-0.631	Destabilizing	0.775	D	0.554	neutral	None	None	None	None	N
K/T	0.1441	likely_benign	0.1629	benign	-0.405	Destabilizing	0.901	D	0.625	neutral	N	0.468537479	None	None	N
K/V	0.2699	likely_benign	0.2946	benign	0.164	Stabilizing	0.633	D	0.57	neutral	None	None	None	None	N
K/W	0.7361	likely_pathogenic	0.7401	pathogenic	-0.259	Destabilizing	0.996	D	0.669	neutral	None	None	None	None	N
K/Y	0.6008	likely_pathogenic	0.6153	pathogenic	0.079	Stabilizing	0.961	D	0.69	prob.neutral	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.