TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33603	101032;101033;101034	chr2:178535808;178535807;178535806	chr2:179400535;179400534;179400533
N2AB	31962	96109;96110;96111	chr2:178535808;178535807;178535806	chr2:179400535;179400534;179400533
N2A	31035	93328;93329;93330	chr2:178535808;178535807;178535806	chr2:179400535;179400534;179400533
N2B	24538	73837;73838;73839	chr2:178535808;178535807;178535806	chr2:179400535;179400534;179400533
Novex-1	24663	74212;74213;74214	chr2:178535808;178535807;178535806	chr2:179400535;179400534;179400533
Novex-2	24730	74413;74414;74415	chr2:178535808;178535807;178535806	chr2:179400535;179400534;179400533
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-159
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.0969
• 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
G/E	None	None	0.99	N	0.531	0.259	0.211220785272	gnomAD-4.0.0	2.74696E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60631E-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
G/A	0.2299	likely_benign	0.232	benign	-0.531	Destabilizing	0.996	D	0.626	neutral	N	0.477429108	None	None	N
G/C	0.6011	likely_pathogenic	0.5418	ambiguous	-0.676	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
G/D	0.4538	ambiguous	0.4361	ambiguous	-1.144	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
G/E	0.3689	ambiguous	0.37	ambiguous	-1.294	Destabilizing	0.99	D	0.531	neutral	N	0.397850817	None	None	N
G/F	0.8846	likely_pathogenic	0.8706	pathogenic	-1.258	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
G/H	0.7749	likely_pathogenic	0.744	pathogenic	-1.149	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
G/I	0.6601	likely_pathogenic	0.6427	pathogenic	-0.507	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
G/K	0.726	likely_pathogenic	0.6958	pathogenic	-1.131	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
G/L	0.749	likely_pathogenic	0.7493	pathogenic	-0.507	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
G/M	0.7658	likely_pathogenic	0.7622	pathogenic	-0.293	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
G/N	0.5423	ambiguous	0.5178	ambiguous	-0.605	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
G/P	0.8473	likely_pathogenic	0.8415	pathogenic	-0.48	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/Q	0.6054	likely_pathogenic	0.595	pathogenic	-0.918	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/R	0.6545	likely_pathogenic	0.6376	pathogenic	-0.706	Destabilizing	1.0	D	0.757	deleterious	N	0.442719102	None	None	N
G/S	0.226	likely_benign	0.2167	benign	-0.682	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
G/T	0.3349	likely_benign	0.3199	benign	-0.78	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/V	0.441	ambiguous	0.4383	ambiguous	-0.48	Destabilizing	1.0	D	0.767	deleterious	N	0.459363422	None	None	N
G/W	0.8268	likely_pathogenic	0.7992	pathogenic	-1.492	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/Y	0.8178	likely_pathogenic	0.7817	pathogenic	-1.14	Destabilizing	1.0	D	0.729	prob.delet.	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.