TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31842	95749;95750;95751	chr2:178545586;178545585;178545584	chr2:179410313;179410312;179410311
N2AB	30201	90826;90827;90828	chr2:178545586;178545585;178545584	chr2:179410313;179410312;179410311
N2A	29274	88045;88046;88047	chr2:178545586;178545585;178545584	chr2:179410313;179410312;179410311
N2B	22777	68554;68555;68556	chr2:178545586;178545585;178545584	chr2:179410313;179410312;179410311
Novex-1	22902	68929;68930;68931	chr2:178545586;178545585;178545584	chr2:179410313;179410312;179410311
Novex-2	22969	69130;69131;69132	chr2:178545586;178545585;178545584	chr2:179410313;179410312;179410311
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-120
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1064
• 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
Y/D	rs1452962684	-3.44	1.0	D	0.896	0.887	0.793836073555	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
Y/D	rs1452962684	-3.44	1.0	D	0.896	0.887	0.793836073555	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79903E-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
Y/A	0.9976	likely_pathogenic	0.9975	pathogenic	-3.742	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
Y/C	0.9487	likely_pathogenic	0.9465	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.866	deleterious	D	0.66371008	None	None	N
Y/D	0.9971	likely_pathogenic	0.9965	pathogenic	-4.027	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.664113688	None	None	N
Y/E	0.9994	likely_pathogenic	0.9993	pathogenic	-3.816	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/F	0.2114	likely_benign	0.2386	benign	-1.648	Destabilizing	0.999	D	0.651	neutral	D	0.593335624	None	None	N
Y/G	0.9942	likely_pathogenic	0.9939	pathogenic	-4.134	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/H	0.9798	likely_pathogenic	0.9771	pathogenic	-2.804	Highly Destabilizing	1.0	D	0.853	deleterious	D	0.66371008	None	None	N
Y/I	0.9617	likely_pathogenic	0.9604	pathogenic	-2.395	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9988	pathogenic	-2.767	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/L	0.9301	likely_pathogenic	0.9198	pathogenic	-2.395	Highly Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
Y/M	0.9851	likely_pathogenic	0.9848	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/N	0.9851	likely_pathogenic	0.982	pathogenic	-3.57	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.664113688	None	None	N
Y/P	0.9993	likely_pathogenic	0.9993	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
Y/Q	0.9987	likely_pathogenic	0.9985	pathogenic	-3.307	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/R	0.9956	likely_pathogenic	0.9951	pathogenic	-2.479	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/S	0.9912	likely_pathogenic	0.9899	pathogenic	-3.856	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.664113688	None	None	N
Y/T	0.9961	likely_pathogenic	0.9954	pathogenic	-3.532	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/V	0.9521	likely_pathogenic	0.9507	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
Y/W	0.8809	likely_pathogenic	0.8741	pathogenic	-0.894	Destabilizing	1.0	D	0.844	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.