TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9579	28960;28961;28962	chr2:178709584;178709583;178709582	chr2:179574311;179574310;179574309
N2AB	9262	28009;28010;28011	chr2:178709584;178709583;178709582	chr2:179574311;179574310;179574309
N2A	8335	25228;25229;25230	chr2:178709584;178709583;178709582	chr2:179574311;179574310;179574309
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-81
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.1277
• 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
S/P	None	None	0.988	None	0.765	0.395	0.45755974854	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
S/A	0.1093	likely_benign	0.0865	benign	-1.244	Destabilizing	0.061	N	0.142	neutral	None	None	None	None	N
S/C	0.2532	likely_benign	0.2384	benign	-0.945	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
S/D	0.9904	likely_pathogenic	0.9884	pathogenic	-0.639	Destabilizing	0.969	D	0.694	prob.neutral	None	None	None	None	N
S/E	0.9939	likely_pathogenic	0.9923	pathogenic	-0.526	Destabilizing	0.969	D	0.649	neutral	None	None	None	None	N
S/F	0.9324	likely_pathogenic	0.8923	pathogenic	-1.39	Destabilizing	0.988	D	0.763	deleterious	None	None	None	None	N
S/G	0.3203	likely_benign	0.2756	benign	-1.542	Destabilizing	0.863	D	0.602	neutral	None	None	None	None	N
S/H	0.9795	likely_pathogenic	0.9738	pathogenic	-1.767	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
S/I	0.793	likely_pathogenic	0.7849	pathogenic	-0.51	Destabilizing	0.884	D	0.672	neutral	None	None	None	None	N
S/K	0.9988	likely_pathogenic	0.9984	pathogenic	-0.277	Destabilizing	0.969	D	0.651	neutral	None	None	None	None	N
S/L	0.5929	likely_pathogenic	0.5654	pathogenic	-0.51	Destabilizing	0.759	D	0.648	neutral	None	None	None	None	N
S/M	0.7962	likely_pathogenic	0.7701	pathogenic	-0.376	Destabilizing	0.991	D	0.746	deleterious	None	None	None	None	N
S/N	0.8925	likely_pathogenic	0.8814	pathogenic	-0.622	Destabilizing	0.969	D	0.675	neutral	None	None	None	None	N
S/P	0.9893	likely_pathogenic	0.9887	pathogenic	-0.726	Destabilizing	0.988	D	0.765	deleterious	None	None	None	None	N
S/Q	0.9883	likely_pathogenic	0.9853	pathogenic	-0.643	Destabilizing	0.997	D	0.709	prob.delet.	None	None	None	None	N
S/R	0.9966	likely_pathogenic	0.9954	pathogenic	-0.405	Destabilizing	0.991	D	0.772	deleterious	None	None	None	None	N
S/T	0.1666	likely_benign	0.172	benign	-0.612	Destabilizing	0.134	N	0.166	neutral	None	None	None	None	N
S/V	0.5876	likely_pathogenic	0.5695	pathogenic	-0.726	Destabilizing	0.079	N	0.424	neutral	None	None	None	None	N
S/W	0.9803	likely_pathogenic	0.9703	pathogenic	-1.328	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
S/Y	0.9379	likely_pathogenic	0.9006	pathogenic	-1.01	Destabilizing	0.996	D	0.768	deleterious	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.