TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15173	45742;45743;45744	chr2:178621201;178621200;178621199	chr2:179485928;179485927;179485926
N2AB	13532	40819;40820;40821	chr2:178621201;178621200;178621199	chr2:179485928;179485927;179485926
N2A	12605	38038;38039;38040	chr2:178621201;178621200;178621199	chr2:179485928;179485927;179485926
N2B	6108	18547;18548;18549	chr2:178621201;178621200;178621199	chr2:179485928;179485927;179485926
Novex-1	6233	18922;18923;18924	chr2:178621201;178621200;178621199	chr2:179485928;179485927;179485926
Novex-2	6300	19123;19124;19125	chr2:178621201;178621200;178621199	chr2:179485928;179485927;179485926
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-103
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.4124
• 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/M	None	None	0.999	D	0.686	0.395	0.468753983522	gnomAD-4.0.0	1.59378E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43373E-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	0.7533	likely_pathogenic	0.6956	pathogenic	-0.539	Destabilizing	0.919	D	0.609	neutral	None	None	None	None	N
K/C	0.8804	likely_pathogenic	0.8396	pathogenic	-0.723	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
K/D	0.8054	likely_pathogenic	0.762	pathogenic	-0.507	Destabilizing	0.988	D	0.676	prob.neutral	None	None	None	None	N
K/E	0.3596	ambiguous	0.3315	benign	-0.42	Destabilizing	0.896	D	0.523	neutral	N	0.507825577	None	None	N
K/F	0.9144	likely_pathogenic	0.8941	pathogenic	-0.427	Destabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
K/G	0.8177	likely_pathogenic	0.7785	pathogenic	-0.882	Destabilizing	0.959	D	0.669	neutral	None	None	None	None	N
K/H	0.4497	ambiguous	0.3987	ambiguous	-1.325	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
K/I	0.5246	ambiguous	0.4813	ambiguous	0.34	Stabilizing	0.976	D	0.747	deleterious	None	None	None	None	N
K/L	0.5755	likely_pathogenic	0.5156	ambiguous	0.34	Stabilizing	0.919	D	0.675	neutral	None	None	None	None	N
K/M	0.3851	ambiguous	0.3439	ambiguous	0.341	Stabilizing	0.999	D	0.686	prob.neutral	D	0.544130408	None	None	N
K/N	0.556	ambiguous	0.5035	ambiguous	-0.612	Destabilizing	0.968	D	0.572	neutral	N	0.512093164	None	None	N
K/P	0.9798	likely_pathogenic	0.9769	pathogenic	0.077	Stabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	N
K/Q	0.1897	likely_benign	0.1734	benign	-0.776	Destabilizing	0.968	D	0.583	neutral	N	0.510637132	None	None	N
K/R	0.0926	likely_benign	0.0861	benign	-0.673	Destabilizing	0.026	N	0.181	neutral	N	0.477579467	None	None	N
K/S	0.7105	likely_pathogenic	0.647	pathogenic	-1.222	Destabilizing	0.851	D	0.497	neutral	None	None	None	None	N
K/T	0.333	likely_benign	0.2827	benign	-0.94	Destabilizing	0.211	N	0.341	neutral	N	0.509280174	None	None	N
K/V	0.5254	ambiguous	0.4789	ambiguous	0.077	Stabilizing	0.976	D	0.675	prob.neutral	None	None	None	None	N
K/W	0.8944	likely_pathogenic	0.867	pathogenic	-0.321	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/Y	0.7767	likely_pathogenic	0.736	pathogenic	0.021	Stabilizing	0.996	D	0.747	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.