TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17025	51298;51299;51300	chr2:178611056;178611055;178611054	chr2:179475783;179475782;179475781
N2AB	15384	46375;46376;46377	chr2:178611056;178611055;178611054	chr2:179475783;179475782;179475781
N2A	14457	43594;43595;43596	chr2:178611056;178611055;178611054	chr2:179475783;179475782;179475781
N2B	7960	24103;24104;24105	chr2:178611056;178611055;178611054	chr2:179475783;179475782;179475781
Novex-1	8085	24478;24479;24480	chr2:178611056;178611055;178611054	chr2:179475783;179475782;179475781
Novex-2	8152	24679;24680;24681	chr2:178611056;178611055;178611054	chr2:179475783;179475782;179475781
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-111
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1502
• 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
Y/C	None	None	1.0	D	0.854	0.793	0.879908228484	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
Y/A	0.9967	likely_pathogenic	0.9966	pathogenic	-2.154	Highly Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
Y/C	0.8825	likely_pathogenic	0.8908	pathogenic	-1.694	Destabilizing	1.0	D	0.854	deleterious	D	0.798223113	None	None	N
Y/D	0.9984	likely_pathogenic	0.998	pathogenic	-2.499	Highly Destabilizing	0.999	D	0.891	deleterious	D	0.798223113	None	None	N
Y/E	0.9993	likely_pathogenic	0.9991	pathogenic	-2.248	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/F	0.1539	likely_benign	0.1927	benign	-0.69	Destabilizing	0.217	N	0.389	neutral	D	0.67955281	None	None	N
Y/G	0.9945	likely_pathogenic	0.9935	pathogenic	-2.616	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/H	0.9485	likely_pathogenic	0.9459	pathogenic	-1.913	Destabilizing	0.999	D	0.699	prob.neutral	D	0.79884746	None	None	N
Y/I	0.9389	likely_pathogenic	0.9538	pathogenic	-0.639	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9987	pathogenic	-1.769	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/L	0.8596	likely_pathogenic	0.8748	pathogenic	-0.639	Destabilizing	0.983	D	0.771	deleterious	None	None	None	None	N
Y/M	0.9737	likely_pathogenic	0.9775	pathogenic	-0.78	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
Y/N	0.9885	likely_pathogenic	0.9852	pathogenic	-2.646	Highly Destabilizing	0.999	D	0.874	deleterious	D	0.798223113	None	None	N
Y/P	0.999	likely_pathogenic	0.9986	pathogenic	-1.158	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.9981	likely_pathogenic	0.9978	pathogenic	-2.182	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
Y/R	0.9945	likely_pathogenic	0.9931	pathogenic	-2.038	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
Y/S	0.9882	likely_pathogenic	0.9856	pathogenic	-3.048	Highly Destabilizing	0.999	D	0.871	deleterious	D	0.798223113	None	None	N
Y/T	0.9953	likely_pathogenic	0.9949	pathogenic	-2.648	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/V	0.9274	likely_pathogenic	0.9404	pathogenic	-1.158	Destabilizing	0.992	D	0.791	deleterious	None	None	None	None	N
Y/W	0.724	likely_pathogenic	0.7561	pathogenic	-0.081	Destabilizing	1.0	D	0.705	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.