TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22195	66808;66809;66810	chr2:178581685;178581684;178581683	chr2:179446412;179446411;179446410
N2AB	20554	61885;61886;61887	chr2:178581685;178581684;178581683	chr2:179446412;179446411;179446410
N2A	19627	59104;59105;59106	chr2:178581685;178581684;178581683	chr2:179446412;179446411;179446410
N2B	13130	39613;39614;39615	chr2:178581685;178581684;178581683	chr2:179446412;179446411;179446410
Novex-1	13255	39988;39989;39990	chr2:178581685;178581684;178581683	chr2:179446412;179446411;179446410
Novex-2	13322	40189;40190;40191	chr2:178581685;178581684;178581683	chr2:179446412;179446411;179446410
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: Fn3-49
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.0726
• 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/L	None	None	0.017	N	0.313	0.045	0.443695250439	gnomAD-4.0.0	1.59442E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88494E-05	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
V/A	0.1808	likely_benign	0.2692	benign	-1.936	Destabilizing	0.001	N	0.153	neutral	N	0.383898163	None	None	N
V/C	0.465	ambiguous	0.5467	ambiguous	-1.166	Destabilizing	0.001	N	0.438	neutral	None	None	None	None	N
V/D	0.9082	likely_pathogenic	0.9365	pathogenic	-3.09	Highly Destabilizing	0.418	N	0.744	deleterious	None	None	None	None	N
V/E	0.7345	likely_pathogenic	0.778	pathogenic	-2.789	Highly Destabilizing	0.351	N	0.744	deleterious	N	0.499954543	None	None	N
V/F	0.1953	likely_benign	0.2119	benign	-1.216	Destabilizing	0.002	N	0.436	neutral	None	None	None	None	N
V/G	0.3118	likely_benign	0.4081	ambiguous	-2.491	Highly Destabilizing	0.101	N	0.693	prob.neutral	N	0.467631481	None	None	N
V/H	0.7951	likely_pathogenic	0.8174	pathogenic	-2.57	Highly Destabilizing	0.836	D	0.761	deleterious	None	None	None	None	N
V/I	0.1188	likely_benign	0.1161	benign	-0.323	Destabilizing	0.101	N	0.431	neutral	N	0.403926719	None	None	N
V/K	0.6923	likely_pathogenic	0.7007	pathogenic	-1.558	Destabilizing	0.418	N	0.743	deleterious	None	None	None	None	N
V/L	0.3272	likely_benign	0.3455	ambiguous	-0.323	Destabilizing	0.017	N	0.313	neutral	N	0.447965498	None	None	N
V/M	0.17	likely_benign	0.1703	benign	-0.465	Destabilizing	0.027	N	0.319	neutral	None	None	None	None	N
V/N	0.7193	likely_pathogenic	0.7952	pathogenic	-2.239	Highly Destabilizing	0.418	N	0.763	deleterious	None	None	None	None	N
V/P	0.9915	likely_pathogenic	0.9938	pathogenic	-0.843	Destabilizing	0.593	D	0.763	deleterious	None	None	None	None	N
V/Q	0.5772	likely_pathogenic	0.6105	pathogenic	-1.902	Destabilizing	0.593	D	0.777	deleterious	None	None	None	None	N
V/R	0.6113	likely_pathogenic	0.6413	pathogenic	-1.723	Destabilizing	0.418	N	0.77	deleterious	None	None	None	None	N
V/S	0.3421	ambiguous	0.4454	ambiguous	-2.636	Highly Destabilizing	0.004	N	0.557	neutral	None	None	None	None	N
V/T	0.3379	likely_benign	0.4085	ambiguous	-2.192	Highly Destabilizing	0.129	N	0.493	neutral	None	None	None	None	N
V/W	0.8794	likely_pathogenic	0.8849	pathogenic	-1.845	Destabilizing	0.94	D	0.761	deleterious	None	None	None	None	N
V/Y	0.4804	ambiguous	0.5099	ambiguous	-1.438	Destabilizing	0.004	N	0.413	neutral	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.