TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16387	49384;49385;49386	chr2:178614238;178614237;178614236	chr2:179478965;179478964;179478963
N2AB	14746	44461;44462;44463	chr2:178614238;178614237;178614236	chr2:179478965;179478964;179478963
N2A	13819	41680;41681;41682	chr2:178614238;178614237;178614236	chr2:179478965;179478964;179478963
N2B	7322	22189;22190;22191	chr2:178614238;178614237;178614236	chr2:179478965;179478964;179478963
Novex-1	7447	22564;22565;22566	chr2:178614238;178614237;178614236	chr2:179478965;179478964;179478963
Novex-2	7514	22765;22766;22767	chr2:178614238;178614237;178614236	chr2:179478965;179478964;179478963
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-6
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1999
• 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
V/A	rs765925142	-2.437	0.104	N	0.634	0.262	0.537262924806	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.65E-05	None	0	None	0	0	0
V/A	rs765925142	-2.437	0.104	N	0.634	0.262	0.537262924806	gnomAD-4.0.0	1.59357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86144E-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
V/A	0.6353	likely_pathogenic	0.545	ambiguous	-2.117	Highly Destabilizing	0.104	N	0.634	neutral	N	0.477055728	None	None	N
V/C	0.8606	likely_pathogenic	0.8203	pathogenic	-1.978	Destabilizing	0.968	D	0.707	prob.neutral	None	None	None	None	N
V/D	0.9224	likely_pathogenic	0.8747	pathogenic	-2.889	Highly Destabilizing	0.667	D	0.782	deleterious	N	0.517694114	None	None	N
V/E	0.8127	likely_pathogenic	0.7473	pathogenic	-2.786	Highly Destabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
V/F	0.4399	ambiguous	0.3953	ambiguous	-1.423	Destabilizing	0.497	N	0.708	prob.delet.	N	0.471485966	None	None	N
V/G	0.8232	likely_pathogenic	0.7482	pathogenic	-2.53	Highly Destabilizing	0.667	D	0.752	deleterious	D	0.586077235	None	None	N
V/H	0.8729	likely_pathogenic	0.8365	pathogenic	-1.978	Destabilizing	0.968	D	0.776	deleterious	None	None	None	None	N
V/I	0.0693	likely_benign	0.0704	benign	-1.01	Destabilizing	None	N	0.238	neutral	N	0.391433545	None	None	N
V/K	0.8282	likely_pathogenic	0.7697	pathogenic	-1.82	Destabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
V/L	0.3976	ambiguous	0.3596	ambiguous	-1.01	Destabilizing	0.009	N	0.448	neutral	N	0.465709643	None	None	N
V/M	0.2902	likely_benign	0.2526	benign	-1.089	Destabilizing	0.567	D	0.703	prob.neutral	None	None	None	None	N
V/N	0.7707	likely_pathogenic	0.698	pathogenic	-1.965	Destabilizing	0.89	D	0.801	deleterious	None	None	None	None	N
V/P	0.9952	likely_pathogenic	0.9931	pathogenic	-1.351	Destabilizing	0.89	D	0.717	prob.delet.	None	None	None	None	N
V/Q	0.759	likely_pathogenic	0.6986	pathogenic	-2.043	Highly Destabilizing	0.89	D	0.735	prob.delet.	None	None	None	None	N
V/R	0.7478	likely_pathogenic	0.6795	pathogenic	-1.342	Destabilizing	0.726	D	0.802	deleterious	None	None	None	None	N
V/S	0.6649	likely_pathogenic	0.582	pathogenic	-2.51	Highly Destabilizing	0.726	D	0.687	prob.neutral	None	None	None	None	N
V/T	0.3977	ambiguous	0.3329	benign	-2.291	Highly Destabilizing	0.272	N	0.653	neutral	None	None	None	None	N
V/W	0.94	likely_pathogenic	0.9255	pathogenic	-1.751	Destabilizing	0.968	D	0.74	deleterious	None	None	None	None	N
V/Y	0.825	likely_pathogenic	0.7806	pathogenic	-1.468	Destabilizing	0.726	D	0.722	prob.delet.	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.