TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7498	22717;22718;22719	chr2:178722295;178722294;178722293	chr2:179587022;179587021;179587020
N2AB	7181	21766;21767;21768	chr2:178722295;178722294;178722293	chr2:179587022;179587021;179587020
N2A	6254	18985;18986;18987	chr2:178722295;178722294;178722293	chr2:179587022;179587021;179587020
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-59
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2273
• 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
G/E	None	None	1.0	D	0.83	0.604	0.879581146893	gnomAD-4.0.0	1.60706E-06	None	None	None	None	I	None	0	0	None	0	2.77654E-05	None	0	0	0	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	0.7951	likely_pathogenic	0.7891	pathogenic	-0.327	Destabilizing	1.0	D	0.746	deleterious	D	0.606413618	None	None	I
G/C	0.9577	likely_pathogenic	0.9522	pathogenic	-0.859	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/D	0.9478	likely_pathogenic	0.9455	pathogenic	-0.615	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/E	0.9601	likely_pathogenic	0.9598	pathogenic	-0.784	Destabilizing	1.0	D	0.83	deleterious	D	0.626642303	None	None	I
G/F	0.9875	likely_pathogenic	0.9857	pathogenic	-1.08	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/H	0.9828	likely_pathogenic	0.9827	pathogenic	-0.589	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/I	0.9856	likely_pathogenic	0.9821	pathogenic	-0.484	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/K	0.986	likely_pathogenic	0.9867	pathogenic	-0.839	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/L	0.9775	likely_pathogenic	0.9762	pathogenic	-0.484	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/M	0.9894	likely_pathogenic	0.9867	pathogenic	-0.494	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/N	0.9679	likely_pathogenic	0.9699	pathogenic	-0.452	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/P	0.998	likely_pathogenic	0.9984	pathogenic	-0.399	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/Q	0.9706	likely_pathogenic	0.9677	pathogenic	-0.753	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/R	0.9622	likely_pathogenic	0.9647	pathogenic	-0.382	Destabilizing	1.0	D	0.857	deleterious	D	0.639088113	None	None	I
G/S	0.7472	likely_pathogenic	0.7481	pathogenic	-0.584	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/T	0.9496	likely_pathogenic	0.9418	pathogenic	-0.686	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/V	0.9654	likely_pathogenic	0.9595	pathogenic	-0.399	Destabilizing	1.0	D	0.832	deleterious	D	0.665433442	None	None	I
G/W	0.9825	likely_pathogenic	0.98	pathogenic	-1.223	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/Y	0.9805	likely_pathogenic	0.9795	pathogenic	-0.882	Destabilizing	1.0	D	0.834	deleterious	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.