TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17339	52240;52241;52242	chr2:178609295;178609294;178609293	chr2:179474022;179474021;179474020
N2AB	15698	47317;47318;47319	chr2:178609295;178609294;178609293	chr2:179474022;179474021;179474020
N2A	14771	44536;44537;44538	chr2:178609295;178609294;178609293	chr2:179474022;179474021;179474020
N2B	8274	25045;25046;25047	chr2:178609295;178609294;178609293	chr2:179474022;179474021;179474020
Novex-1	8399	25420;25421;25422	chr2:178609295;178609294;178609293	chr2:179474022;179474021;179474020
Novex-2	8466	25621;25622;25623	chr2:178609295;178609294;178609293	chr2:179474022;179474021;179474020
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-112
• Domain position: 89
• Structural Position: 144
• Q(SASA): 0.1281
• 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/T	rs765426395	None	0.978	N	0.529	0.153	0.292062946507	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
S/Y	None	None	0.999	N	0.773	0.469	0.806415548049	gnomAD-4.0.0	1.62947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.49504E-05	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	0.0804	likely_benign	0.0792	benign	-0.547	Destabilizing	0.37	N	0.312	neutral	N	0.429406741	None	None	N
S/C	0.0829	likely_benign	0.0863	benign	-1.019	Destabilizing	1.0	D	0.739	prob.delet.	N	0.489017978	None	None	N
S/D	0.9895	likely_pathogenic	0.9883	pathogenic	-2.445	Highly Destabilizing	0.992	D	0.651	neutral	None	None	None	None	N
S/E	0.992	likely_pathogenic	0.9913	pathogenic	-2.301	Highly Destabilizing	0.992	D	0.635	neutral	None	None	None	None	N
S/F	0.9611	likely_pathogenic	0.95	pathogenic	-0.589	Destabilizing	0.999	D	0.767	deleterious	N	0.501581766	None	None	N
S/G	0.3022	likely_benign	0.2762	benign	-0.842	Destabilizing	0.967	D	0.539	neutral	None	None	None	None	N
S/H	0.9797	likely_pathogenic	0.975	pathogenic	-1.287	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
S/I	0.5927	likely_pathogenic	0.5704	pathogenic	0.162	Stabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
S/K	0.9978	likely_pathogenic	0.9976	pathogenic	-0.687	Destabilizing	0.983	D	0.634	neutral	None	None	None	None	N
S/L	0.575	likely_pathogenic	0.5428	ambiguous	0.162	Stabilizing	0.983	D	0.682	prob.neutral	None	None	None	None	N
S/M	0.7839	likely_pathogenic	0.7722	pathogenic	0.015	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
S/N	0.8881	likely_pathogenic	0.8836	pathogenic	-1.463	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
S/P	0.8654	likely_pathogenic	0.8424	pathogenic	-0.042	Destabilizing	0.997	D	0.743	deleterious	D	0.525016064	None	None	N
S/Q	0.9865	likely_pathogenic	0.9853	pathogenic	-1.353	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
S/R	0.9937	likely_pathogenic	0.9928	pathogenic	-0.825	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
S/T	0.1428	likely_benign	0.1507	benign	-0.973	Destabilizing	0.978	D	0.529	neutral	N	0.474395243	None	None	N
S/V	0.3817	ambiguous	0.3873	ambiguous	-0.042	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
S/W	0.9894	likely_pathogenic	0.9859	pathogenic	-0.987	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
S/Y	0.9696	likely_pathogenic	0.9606	pathogenic	-0.49	Destabilizing	0.999	D	0.773	deleterious	N	0.501835255	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.