TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22964	69115;69116;69117	chr2:178577445;178577444;178577443	chr2:179442172;179442171;179442170
N2AB	21323	64192;64193;64194	chr2:178577445;178577444;178577443	chr2:179442172;179442171;179442170
N2A	20396	61411;61412;61413	chr2:178577445;178577444;178577443	chr2:179442172;179442171;179442170
N2B	13899	41920;41921;41922	chr2:178577445;178577444;178577443	chr2:179442172;179442171;179442170
Novex-1	14024	42295;42296;42297	chr2:178577445;178577444;178577443	chr2:179442172;179442171;179442170
Novex-2	14091	42496;42497;42498	chr2:178577445;178577444;178577443	chr2:179442172;179442171;179442170
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-128
• Domain position: 15
• Structural Position: 28
• Q(SASA): 0.3361
• Predicted PPI site: I

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
I/T	None	None	0.892	N	0.546	0.316	0.518858945281	gnomAD-4.0.0	1.37371E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80449E-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
I/A	0.6156	likely_pathogenic	0.5646	pathogenic	-2.752	Highly Destabilizing	0.845	D	0.421	neutral	None	None	None	None	I
I/C	0.9035	likely_pathogenic	0.8933	pathogenic	-2.027	Highly Destabilizing	0.999	D	0.582	neutral	None	None	None	None	I
I/D	0.9953	likely_pathogenic	0.9965	pathogenic	-3.151	Highly Destabilizing	0.996	D	0.672	neutral	None	None	None	None	I
I/E	0.989	likely_pathogenic	0.9915	pathogenic	-2.867	Highly Destabilizing	0.987	D	0.671	neutral	None	None	None	None	I
I/F	0.3568	ambiguous	0.3089	benign	-1.668	Destabilizing	0.967	D	0.571	neutral	N	0.509234882	None	None	I
I/G	0.9654	likely_pathogenic	0.9663	pathogenic	-3.354	Highly Destabilizing	0.987	D	0.663	neutral	None	None	None	None	I
I/H	0.9813	likely_pathogenic	0.9819	pathogenic	-2.783	Highly Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
I/K	0.9724	likely_pathogenic	0.9768	pathogenic	-2.25	Highly Destabilizing	0.987	D	0.671	neutral	None	None	None	None	I
I/L	0.1513	likely_benign	0.1559	benign	-0.979	Destabilizing	0.426	N	0.313	neutral	N	0.472175217	None	None	I
I/M	0.1549	likely_benign	0.1502	benign	-0.922	Destabilizing	0.983	D	0.567	neutral	N	0.48025483	None	None	I
I/N	0.9533	likely_pathogenic	0.964	pathogenic	-2.77	Highly Destabilizing	0.994	D	0.683	prob.neutral	N	0.507259855	None	None	I
I/P	0.9828	likely_pathogenic	0.9834	pathogenic	-1.555	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	I
I/Q	0.9782	likely_pathogenic	0.9804	pathogenic	-2.529	Highly Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	I
I/R	0.9562	likely_pathogenic	0.9618	pathogenic	-2.079	Highly Destabilizing	0.987	D	0.684	prob.neutral	None	None	None	None	I
I/S	0.894	likely_pathogenic	0.8965	pathogenic	-3.477	Highly Destabilizing	0.967	D	0.61	neutral	N	0.488902111	None	None	I
I/T	0.7076	likely_pathogenic	0.6789	pathogenic	-3.024	Highly Destabilizing	0.892	D	0.546	neutral	N	0.514968776	None	None	I
I/V	0.0832	likely_benign	0.0783	benign	-1.555	Destabilizing	0.011	N	0.188	neutral	N	0.430864525	None	None	I
I/W	0.9806	likely_pathogenic	0.9769	pathogenic	-2.049	Highly Destabilizing	0.999	D	0.626	neutral	None	None	None	None	I
I/Y	0.9116	likely_pathogenic	0.9068	pathogenic	-1.771	Destabilizing	0.987	D	0.597	neutral	None	None	None	None	I

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.