TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17648	53167;53168;53169	chr2:178607845;178607844;178607843	chr2:179472572;179472571;179472570
N2AB	16007	48244;48245;48246	chr2:178607845;178607844;178607843	chr2:179472572;179472571;179472570
N2A	15080	45463;45464;45465	chr2:178607845;178607844;178607843	chr2:179472572;179472571;179472570
N2B	8583	25972;25973;25974	chr2:178607845;178607844;178607843	chr2:179472572;179472571;179472570
Novex-1	8708	26347;26348;26349	chr2:178607845;178607844;178607843	chr2:179472572;179472571;179472570
Novex-2	8775	26548;26549;26550	chr2:178607845;178607844;178607843	chr2:179472572;179472571;179472570
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-16
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.1177
• 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
N/S	rs752142832	-0.782	0.999	N	0.589	0.512	0.224531998449	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
N/S	rs752142832	-0.782	0.999	N	0.589	0.512	0.224531998449	gnomAD-4.0.0	6.16042E-06	None	None	None	None	N	None	0	2.23704E-05	None	0	0	None	0	0	7.19802E-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
N/A	0.9898	likely_pathogenic	0.9874	pathogenic	-0.27	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
N/C	0.9032	likely_pathogenic	0.9118	pathogenic	-0.357	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
N/D	0.9782	likely_pathogenic	0.9693	pathogenic	-2.252	Highly Destabilizing	0.999	D	0.609	neutral	N	0.521767529	None	None	N
N/E	0.9973	likely_pathogenic	0.9971	pathogenic	-2.121	Highly Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
N/F	0.9979	likely_pathogenic	0.9978	pathogenic	-0.41	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
N/G	0.9777	likely_pathogenic	0.9747	pathogenic	-0.554	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
N/H	0.9561	likely_pathogenic	0.9534	pathogenic	-0.446	Destabilizing	1.0	D	0.779	deleterious	D	0.533630814	None	None	N
N/I	0.9833	likely_pathogenic	0.9813	pathogenic	0.428	Stabilizing	1.0	D	0.778	deleterious	D	0.533884303	None	None	N
N/K	0.997	likely_pathogenic	0.9966	pathogenic	-0.04	Destabilizing	1.0	D	0.749	deleterious	D	0.532870345	None	None	N
N/L	0.9473	likely_pathogenic	0.951	pathogenic	0.428	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
N/M	0.9812	likely_pathogenic	0.9806	pathogenic	0.662	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
N/P	0.9947	likely_pathogenic	0.9939	pathogenic	0.224	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
N/Q	0.9963	likely_pathogenic	0.9962	pathogenic	-1.078	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
N/R	0.9946	likely_pathogenic	0.9944	pathogenic	0.026	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
N/S	0.6553	likely_pathogenic	0.6445	pathogenic	-0.787	Destabilizing	0.999	D	0.589	neutral	N	0.490025563	None	None	N
N/T	0.8207	likely_pathogenic	0.8409	pathogenic	-0.514	Destabilizing	0.999	D	0.712	prob.delet.	N	0.487187953	None	None	N
N/V	0.9779	likely_pathogenic	0.976	pathogenic	0.224	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
N/W	0.9994	likely_pathogenic	0.9992	pathogenic	-0.468	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
N/Y	0.9878	likely_pathogenic	0.9859	pathogenic	0.031	Stabilizing	1.0	D	0.79	deleterious	D	0.533123835	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.