TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5573	16942;16943;16944	chr2:178732252;178732251;178732250	chr2:179596979;179596978;179596977
N2AB	5256	15991;15992;15993	chr2:178732252;178732251;178732250	chr2:179596979;179596978;179596977
N2A	4329	13210;13211;13212	chr2:178732252;178732251;178732250	chr2:179596979;179596978;179596977
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-39
• Domain position: 31
• Structural Position: 44
• Q(SASA): 0.134
• 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
I/S	None	None	0.998	N	0.685	0.5	0.895925552087	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
I/A	0.7554	likely_pathogenic	0.8125	pathogenic	-2.161	Highly Destabilizing	0.992	D	0.485	neutral	None	None	None	None	N
I/C	0.9191	likely_pathogenic	0.9398	pathogenic	-1.516	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
I/D	0.9837	likely_pathogenic	0.9871	pathogenic	-1.756	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
I/E	0.9408	likely_pathogenic	0.9497	pathogenic	-1.634	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
I/F	0.5216	ambiguous	0.5467	ambiguous	-1.37	Destabilizing	0.998	D	0.631	neutral	N	0.490567855	None	None	N
I/G	0.942	likely_pathogenic	0.9588	pathogenic	-2.617	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
I/H	0.9483	likely_pathogenic	0.959	pathogenic	-1.935	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
I/K	0.8675	likely_pathogenic	0.8903	pathogenic	-1.563	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
I/L	0.1677	likely_benign	0.1806	benign	-0.911	Destabilizing	0.889	D	0.408	neutral	N	0.499442829	None	None	N
I/M	0.1757	likely_benign	0.1926	benign	-0.825	Destabilizing	0.998	D	0.603	neutral	N	0.501924161	None	None	N
I/N	0.8474	likely_pathogenic	0.8712	pathogenic	-1.597	Destabilizing	0.999	D	0.759	deleterious	D	0.528929186	None	None	N
I/P	0.8244	likely_pathogenic	0.8705	pathogenic	-1.301	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
I/Q	0.8733	likely_pathogenic	0.8957	pathogenic	-1.609	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
I/R	0.8209	likely_pathogenic	0.8494	pathogenic	-1.144	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
I/S	0.8424	likely_pathogenic	0.88	pathogenic	-2.329	Highly Destabilizing	0.998	D	0.685	prob.neutral	N	0.488922014	None	None	N
I/T	0.8083	likely_pathogenic	0.8536	pathogenic	-2.068	Highly Destabilizing	0.989	D	0.639	neutral	N	0.494188706	None	None	N
I/V	0.1023	likely_benign	0.1087	benign	-1.301	Destabilizing	0.333	N	0.204	neutral	N	0.481818443	None	None	N
I/W	0.9629	likely_pathogenic	0.9686	pathogenic	-1.577	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
I/Y	0.8963	likely_pathogenic	0.9023	pathogenic	-1.313	Destabilizing	1.0	D	0.699	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.