TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27280	82063;82064;82065	chr2:178564294;178564293;178564292	chr2:179429021;179429020;179429019
N2AB	25639	77140;77141;77142	chr2:178564294;178564293;178564292	chr2:179429021;179429020;179429019
N2A	24712	74359;74360;74361	chr2:178564294;178564293;178564292	chr2:179429021;179429020;179429019
N2B	18215	54868;54869;54870	chr2:178564294;178564293;178564292	chr2:179429021;179429020;179429019
Novex-1	18340	55243;55244;55245	chr2:178564294;178564293;178564292	chr2:179429021;179429020;179429019
Novex-2	18407	55444;55445;55446	chr2:178564294;178564293;178564292	chr2:179429021;179429020;179429019
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-140
• Domain position: 3
• Structural Position: 6
• Q(SASA): 0.7636
• 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/T	None	None	0.942	N	0.566	0.355	0.426787303895	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.2945	likely_benign	0.3039	benign	-0.497	Destabilizing	0.86	D	0.615	neutral	None	None	None	None	N
K/C	0.6781	likely_pathogenic	0.7336	pathogenic	-0.507	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
K/D	0.6107	likely_pathogenic	0.6381	pathogenic	-0.289	Destabilizing	0.956	D	0.608	neutral	None	None	None	None	N
K/E	0.2423	likely_benign	0.2409	benign	-0.177	Destabilizing	0.822	D	0.635	neutral	N	0.497402601	None	None	N
K/F	0.7972	likely_pathogenic	0.8275	pathogenic	-0.277	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
K/G	0.4811	ambiguous	0.5062	ambiguous	-0.826	Destabilizing	0.956	D	0.515	neutral	None	None	None	None	N
K/H	0.3523	ambiguous	0.3862	ambiguous	-1.048	Destabilizing	0.994	D	0.605	neutral	None	None	None	None	N
K/I	0.3406	ambiguous	0.3541	ambiguous	0.344	Stabilizing	0.971	D	0.639	neutral	N	0.512467091	None	None	N
K/L	0.3736	ambiguous	0.399	ambiguous	0.344	Stabilizing	0.956	D	0.515	neutral	None	None	None	None	N
K/M	0.2672	likely_benign	0.2811	benign	-0.018	Destabilizing	0.998	D	0.608	neutral	None	None	None	None	N
K/N	0.485	ambiguous	0.5148	ambiguous	-0.473	Destabilizing	0.942	D	0.617	neutral	N	0.499678754	None	None	N
K/P	0.827	likely_pathogenic	0.8541	pathogenic	0.092	Stabilizing	0.993	D	0.593	neutral	None	None	None	None	N
K/Q	0.1552	likely_benign	0.1576	benign	-0.442	Destabilizing	0.942	D	0.621	neutral	N	0.51158262	None	None	N
K/R	0.0791	likely_benign	0.0793	benign	-0.508	Destabilizing	0.014	N	0.35	neutral	N	0.51560436	None	None	N
K/S	0.4208	ambiguous	0.4424	ambiguous	-0.959	Destabilizing	0.86	D	0.609	neutral	None	None	None	None	N
K/T	0.2023	likely_benign	0.2117	benign	-0.651	Destabilizing	0.942	D	0.566	neutral	N	0.484701597	None	None	N
K/V	0.3046	likely_benign	0.3201	benign	0.092	Stabilizing	0.978	D	0.599	neutral	None	None	None	None	N
K/W	0.8123	likely_pathogenic	0.8436	pathogenic	-0.277	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
K/Y	0.6653	likely_pathogenic	0.7149	pathogenic	0.014	Stabilizing	0.993	D	0.601	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.