TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15594	47005;47006;47007	chr2:178618770;178618769;178618768	chr2:179483497;179483496;179483495
N2AB	13953	42082;42083;42084	chr2:178618770;178618769;178618768	chr2:179483497;179483496;179483495
N2A	13026	39301;39302;39303	chr2:178618770;178618769;178618768	chr2:179483497;179483496;179483495
N2B	6529	19810;19811;19812	chr2:178618770;178618769;178618768	chr2:179483497;179483496;179483495
Novex-1	6654	20185;20186;20187	chr2:178618770;178618769;178618768	chr2:179483497;179483496;179483495
Novex-2	6721	20386;20387;20388	chr2:178618770;178618769;178618768	chr2:179483497;179483496;179483495
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: Ig-108
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.7503
• 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/H	rs727504196	0.625	0.908	N	0.644	0.432	0.473458370588	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
Y/H	rs727504196	0.625	0.908	N	0.644	0.432	0.473458370588	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/H	rs727504196	0.625	0.908	N	0.644	0.432	0.473458370588	gnomAD-4.0.0	2.35807E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.22379E-05	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	0.6845	likely_pathogenic	0.7116	pathogenic	-0.191	Destabilizing	0.648	D	0.582	neutral	None	None	None	None	N
Y/C	0.291	likely_benign	0.3538	ambiguous	0.264	Stabilizing	0.991	D	0.704	prob.neutral	N	0.507158356	None	None	N
Y/D	0.7035	likely_pathogenic	0.7196	pathogenic	0.647	Stabilizing	0.968	D	0.672	neutral	N	0.502594509	None	None	N
Y/E	0.874	likely_pathogenic	0.8791	pathogenic	0.612	Stabilizing	0.929	D	0.642	neutral	None	None	None	None	N
Y/F	0.0997	likely_benign	0.1046	benign	-0.184	Destabilizing	0.004	N	0.383	neutral	N	0.499072437	None	None	N
Y/G	0.7859	likely_pathogenic	0.8064	pathogenic	-0.326	Destabilizing	0.929	D	0.641	neutral	None	None	None	None	N
Y/H	0.3017	likely_benign	0.3419	ambiguous	0.39	Stabilizing	0.908	D	0.644	neutral	N	0.50695778	None	None	N
Y/I	0.5519	ambiguous	0.6028	pathogenic	0.118	Stabilizing	0.764	D	0.616	neutral	None	None	None	None	N
Y/K	0.8134	likely_pathogenic	0.8147	pathogenic	0.383	Stabilizing	0.929	D	0.643	neutral	None	None	None	None	N
Y/L	0.5891	likely_pathogenic	0.6202	pathogenic	0.118	Stabilizing	0.48	N	0.621	neutral	None	None	None	None	N
Y/M	0.7436	likely_pathogenic	0.76	pathogenic	-0.003	Destabilizing	0.98	D	0.662	neutral	None	None	None	None	N
Y/N	0.3967	ambiguous	0.4063	ambiguous	0.173	Stabilizing	0.968	D	0.665	neutral	N	0.502594509	None	None	N
Y/P	0.9439	likely_pathogenic	0.939	pathogenic	0.033	Stabilizing	0.976	D	0.68	prob.neutral	None	None	None	None	N
Y/Q	0.7484	likely_pathogenic	0.7637	pathogenic	0.233	Stabilizing	0.976	D	0.671	neutral	None	None	None	None	N
Y/R	0.6766	likely_pathogenic	0.6918	pathogenic	0.47	Stabilizing	0.929	D	0.667	neutral	None	None	None	None	N
Y/S	0.352	ambiguous	0.3656	ambiguous	-0.083	Destabilizing	0.908	D	0.643	neutral	N	0.50160857	None	None	N
Y/T	0.6407	likely_pathogenic	0.6602	pathogenic	-0.033	Destabilizing	0.929	D	0.647	neutral	None	None	None	None	N
Y/V	0.4769	ambiguous	0.5172	ambiguous	0.033	Stabilizing	0.48	N	0.621	neutral	None	None	None	None	N
Y/W	0.4017	ambiguous	0.4608	ambiguous	-0.463	Destabilizing	0.98	D	0.637	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.