TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8634	26125;26126;26127	chr2:178715514;178715513;178715512	chr2:179580241;179580240;179580239
N2AB	8317	25174;25175;25176	chr2:178715514;178715513;178715512	chr2:179580241;179580240;179580239
N2A	7390	22393;22394;22395	chr2:178715514;178715513;178715512	chr2:179580241;179580240;179580239
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-71
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.3343
• 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/C	rs769050572	-0.212	0.827	D	0.771	0.519	0.628150982837	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.67094E-04	None	0	None	0	0	0
S/C	rs769050572	-0.212	0.827	D	0.771	0.519	0.628150982837	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92678E-04	None	0	0	0	0	0
S/C	rs769050572	-0.212	0.827	D	0.771	0.519	0.628150982837	gnomAD-4.0.0	3.10148E-06	None	None	None	None	N	None	0	0	None	0	1.11488E-04	None	0	0	0	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	0.123	likely_benign	0.1144	benign	-0.608	Destabilizing	0.004	N	0.483	neutral	None	None	None	None	N
S/C	0.2948	likely_benign	0.2246	benign	-0.334	Destabilizing	0.827	D	0.771	deleterious	D	0.543327365	None	None	N
S/D	0.7937	likely_pathogenic	0.718	pathogenic	-0.435	Destabilizing	0.191	N	0.599	neutral	None	None	None	None	N
S/E	0.8313	likely_pathogenic	0.7542	pathogenic	-0.519	Destabilizing	0.248	N	0.584	neutral	None	None	None	None	N
S/F	0.3238	likely_benign	0.2758	benign	-1.31	Destabilizing	0.862	D	0.812	deleterious	None	None	None	None	N
S/G	0.1808	likely_benign	0.1426	benign	-0.709	Destabilizing	0.248	N	0.544	neutral	N	0.505028487	None	None	N
S/H	0.5917	likely_pathogenic	0.4812	ambiguous	-1.397	Destabilizing	0.986	D	0.766	deleterious	None	None	None	None	N
S/I	0.3449	ambiguous	0.2977	benign	-0.459	Destabilizing	0.538	D	0.791	deleterious	N	0.51047299	None	None	N
S/K	0.8702	likely_pathogenic	0.7773	pathogenic	-0.5	Destabilizing	0.468	N	0.584	neutral	None	None	None	None	N
S/L	0.1719	likely_benign	0.1573	benign	-0.459	Destabilizing	0.306	N	0.688	prob.neutral	None	None	None	None	N
S/M	0.3343	likely_benign	0.3103	benign	0.104	Stabilizing	0.959	D	0.771	deleterious	None	None	None	None	N
S/N	0.346	ambiguous	0.284	benign	-0.309	Destabilizing	0.02	N	0.584	neutral	N	0.488556847	None	None	N
S/P	0.7751	likely_pathogenic	0.7002	pathogenic	-0.483	Destabilizing	0.626	D	0.775	deleterious	None	None	None	None	N
S/Q	0.7373	likely_pathogenic	0.6317	pathogenic	-0.683	Destabilizing	0.862	D	0.715	prob.delet.	None	None	None	None	N
S/R	0.804	likely_pathogenic	0.6842	pathogenic	-0.282	Destabilizing	0.7	D	0.781	deleterious	N	0.486897779	None	None	N
S/T	0.1119	likely_benign	0.0968	benign	-0.373	Destabilizing	None	N	0.414	neutral	N	0.501677844	None	None	N
S/V	0.3093	likely_benign	0.2662	benign	-0.483	Destabilizing	0.366	N	0.742	deleterious	None	None	None	None	N
S/W	0.6024	likely_pathogenic	0.4933	ambiguous	-1.274	Destabilizing	0.986	D	0.762	deleterious	None	None	None	None	N
S/Y	0.3547	ambiguous	0.29	benign	-0.988	Destabilizing	0.862	D	0.809	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.