TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20260	61003;61004;61005	chr2:178590947;178590946;178590945	chr2:179455674;179455673;179455672
N2AB	18619	56080;56081;56082	chr2:178590947;178590946;178590945	chr2:179455674;179455673;179455672
N2A	17692	53299;53300;53301	chr2:178590947;178590946;178590945	chr2:179455674;179455673;179455672
N2B	11195	33808;33809;33810	chr2:178590947;178590946;178590945	chr2:179455674;179455673;179455672
Novex-1	11320	34183;34184;34185	chr2:178590947;178590946;178590945	chr2:179455674;179455673;179455672
Novex-2	11387	34384;34385;34386	chr2:178590947;178590946;178590945	chr2:179455674;179455673;179455672
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-34
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.2635
• 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/F	None	None	0.999	D	0.9	0.385	0.761728025676	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8603E-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	0.3321	likely_benign	0.4084	ambiguous	-0.598	Destabilizing	0.994	D	0.522	neutral	D	0.524375772	None	None	N
S/C	0.3047	likely_benign	0.3718	ambiguous	-0.28	Destabilizing	1.0	D	0.843	deleterious	D	0.528948277	None	None	N
S/D	0.9571	likely_pathogenic	0.9659	pathogenic	0.071	Stabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
S/E	0.9868	likely_pathogenic	0.9911	pathogenic	0.167	Stabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
S/F	0.9179	likely_pathogenic	0.9595	pathogenic	-0.613	Destabilizing	0.999	D	0.9	deleterious	D	0.528694787	None	None	N
S/G	0.3709	ambiguous	0.4573	ambiguous	-0.933	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
S/H	0.9362	likely_pathogenic	0.9526	pathogenic	-1.253	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
S/I	0.8556	likely_pathogenic	0.914	pathogenic	0.211	Stabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
S/K	0.9964	likely_pathogenic	0.9975	pathogenic	-0.121	Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
S/L	0.6664	likely_pathogenic	0.7818	pathogenic	0.211	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
S/M	0.7797	likely_pathogenic	0.829	pathogenic	0.183	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
S/N	0.8549	likely_pathogenic	0.8926	pathogenic	-0.399	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
S/P	0.9778	likely_pathogenic	0.9919	pathogenic	-0.022	Destabilizing	0.999	D	0.85	deleterious	D	0.525415922	None	None	N
S/Q	0.9792	likely_pathogenic	0.9832	pathogenic	-0.304	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
S/R	0.9929	likely_pathogenic	0.9958	pathogenic	-0.325	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
S/T	0.2588	likely_benign	0.2897	benign	-0.33	Destabilizing	0.997	D	0.704	prob.delet.	N	0.469330566	None	None	N
S/V	0.7819	likely_pathogenic	0.8534	pathogenic	-0.022	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
S/W	0.9499	likely_pathogenic	0.9751	pathogenic	-0.686	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
S/Y	0.9114	likely_pathogenic	0.9545	pathogenic	-0.308	Destabilizing	0.999	D	0.913	deleterious	D	0.528441298	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.