TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30067	90424;90425;90426	chr2:178552701;178552700;178552699	chr2:179417428;179417427;179417426
N2AB	28426	85501;85502;85503	chr2:178552701;178552700;178552699	chr2:179417428;179417427;179417426
N2A	27499	82720;82721;82722	chr2:178552701;178552700;178552699	chr2:179417428;179417427;179417426
N2B	21002	63229;63230;63231	chr2:178552701;178552700;178552699	chr2:179417428;179417427;179417426
Novex-1	21127	63604;63605;63606	chr2:178552701;178552700;178552699	chr2:179417428;179417427;179417426
Novex-2	21194	63805;63806;63807	chr2:178552701;178552700;178552699	chr2:179417428;179417427;179417426
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-107
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0993
• 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/I	rs747129423	-0.118	0.004	N	0.215	0.12	0.389126455913	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/I	rs747129423	-0.118	0.004	N	0.215	0.12	0.389126455913	gnomAD-4.0.0	1.59104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02334E-05

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	0.4698	ambiguous	0.3745	ambiguous	-2.291	Highly Destabilizing	0.78	D	0.613	neutral	D	0.530779291	None	None	N
V/C	0.9184	likely_pathogenic	0.8969	pathogenic	-1.798	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.995	pathogenic	-3.329	Highly Destabilizing	0.996	D	0.86	deleterious	None	None	None	None	N
V/E	0.9895	likely_pathogenic	0.9852	pathogenic	-3.035	Highly Destabilizing	0.995	D	0.806	deleterious	D	0.542896065	None	None	N
V/F	0.7483	likely_pathogenic	0.6821	pathogenic	-1.332	Destabilizing	0.976	D	0.714	prob.delet.	None	None	None	None	N
V/G	0.8559	likely_pathogenic	0.8034	pathogenic	-2.884	Highly Destabilizing	0.995	D	0.811	deleterious	D	0.542896065	None	None	N
V/H	0.9959	likely_pathogenic	0.9939	pathogenic	-2.813	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
V/I	0.0901	likely_benign	0.0824	benign	-0.584	Destabilizing	0.004	N	0.215	neutral	N	0.43459913	None	None	N
V/K	0.9927	likely_pathogenic	0.9903	pathogenic	-2.071	Highly Destabilizing	0.988	D	0.809	deleterious	None	None	None	None	N
V/L	0.4436	ambiguous	0.3873	ambiguous	-0.584	Destabilizing	0.437	N	0.362	neutral	N	0.505560725	None	None	N
V/M	0.5358	ambiguous	0.4454	ambiguous	-0.727	Destabilizing	0.976	D	0.642	neutral	None	None	None	None	N
V/N	0.9902	likely_pathogenic	0.9845	pathogenic	-2.658	Highly Destabilizing	0.996	D	0.866	deleterious	None	None	None	None	N
V/P	0.9837	likely_pathogenic	0.9787	pathogenic	-1.131	Destabilizing	0.996	D	0.839	deleterious	None	None	None	None	N
V/Q	0.9865	likely_pathogenic	0.9808	pathogenic	-2.354	Highly Destabilizing	0.996	D	0.854	deleterious	None	None	None	None	N
V/R	0.9841	likely_pathogenic	0.9796	pathogenic	-2.038	Highly Destabilizing	0.996	D	0.869	deleterious	None	None	None	None	N
V/S	0.9044	likely_pathogenic	0.8592	pathogenic	-3.189	Highly Destabilizing	0.988	D	0.769	deleterious	None	None	None	None	N
V/T	0.6201	likely_pathogenic	0.5295	ambiguous	-2.744	Highly Destabilizing	0.919	D	0.588	neutral	None	None	None	None	N
V/W	0.9933	likely_pathogenic	0.9901	pathogenic	-1.987	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9795	likely_pathogenic	0.9701	pathogenic	-1.599	Destabilizing	0.996	D	0.745	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.