TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2932	9019;9020;9021	chr2:178769787;178769786;178769785	chr2:179634514;179634513;179634512
N2AB	2932	9019;9020;9021	chr2:178769787;178769786;178769785	chr2:179634514;179634513;179634512
N2A	2932	9019;9020;9021	chr2:178769787;178769786;178769785	chr2:179634514;179634513;179634512
N2B	2886	8881;8882;8883	chr2:178769787;178769786;178769785	chr2:179634514;179634513;179634512
Novex-1	2886	8881;8882;8883	chr2:178769787;178769786;178769785	chr2:179634514;179634513;179634512
Novex-2	2886	8881;8882;8883	chr2:178769787;178769786;178769785	chr2:179634514;179634513;179634512
Novex-3	2932	9019;9020;9021	chr2:178769787;178769786;178769785	chr2:179634514;179634513;179634512

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-19
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.3312
• 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
Q/R	rs1490705975	0.568	0.997	N	0.501	0.468	0.263612267334	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
Q/R	rs1490705975	0.568	0.997	N	0.501	0.468	0.263612267334	gnomAD-4.0.0	1.59048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85652E-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
Q/A	0.5569	ambiguous	0.5034	ambiguous	-0.049	Destabilizing	0.997	D	0.515	neutral	None	None	None	None	N
Q/C	0.9698	likely_pathogenic	0.9494	pathogenic	-0.019	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
Q/D	0.7883	likely_pathogenic	0.7078	pathogenic	0.185	Stabilizing	0.997	D	0.497	neutral	None	None	None	None	N
Q/E	0.1945	likely_benign	0.1451	benign	0.171	Stabilizing	0.992	D	0.413	neutral	N	0.444687768	None	None	N
Q/F	0.9634	likely_pathogenic	0.9527	pathogenic	-0.265	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
Q/G	0.7333	likely_pathogenic	0.6703	pathogenic	-0.228	Destabilizing	0.997	D	0.474	neutral	None	None	None	None	N
Q/H	0.6666	likely_pathogenic	0.5866	pathogenic	0.005	Stabilizing	0.999	D	0.546	neutral	N	0.512119051	None	None	N
Q/I	0.839	likely_pathogenic	0.8073	pathogenic	0.331	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
Q/K	0.3179	likely_benign	0.2412	benign	0.159	Stabilizing	0.997	D	0.487	neutral	N	0.485115069	None	None	N
Q/L	0.5157	ambiguous	0.4195	ambiguous	0.331	Stabilizing	0.997	D	0.474	neutral	N	0.510829366	None	None	N
Q/M	0.7173	likely_pathogenic	0.6823	pathogenic	0.283	Stabilizing	0.999	D	0.547	neutral	None	None	None	None	N
Q/N	0.6168	likely_pathogenic	0.5573	ambiguous	-0.336	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	N
Q/P	0.946	likely_pathogenic	0.8929	pathogenic	0.233	Stabilizing	0.999	D	0.547	neutral	D	0.583073558	None	None	N
Q/R	0.3512	ambiguous	0.2775	benign	0.298	Stabilizing	0.997	D	0.501	neutral	N	0.505132299	None	None	N
Q/S	0.5446	ambiguous	0.4986	ambiguous	-0.301	Destabilizing	0.997	D	0.476	neutral	None	None	None	None	N
Q/T	0.5428	ambiguous	0.4882	ambiguous	-0.157	Destabilizing	0.999	D	0.516	neutral	None	None	None	None	N
Q/V	0.6959	likely_pathogenic	0.6652	pathogenic	0.233	Stabilizing	0.999	D	0.497	neutral	None	None	None	None	N
Q/W	0.9486	likely_pathogenic	0.9217	pathogenic	-0.288	Destabilizing	1.0	D	0.582	neutral	None	None	None	None	N
Q/Y	0.9207	likely_pathogenic	0.886	pathogenic	0.004	Stabilizing	0.999	D	0.539	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.