TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32355	97288;97289;97290	chr2:178542791;178542790;178542789	chr2:179407518;179407517;179407516
N2AB	30714	92365;92366;92367	chr2:178542791;178542790;178542789	chr2:179407518;179407517;179407516
N2A	29787	89584;89585;89586	chr2:178542791;178542790;178542789	chr2:179407518;179407517;179407516
N2B	23290	70093;70094;70095	chr2:178542791;178542790;178542789	chr2:179407518;179407517;179407516
Novex-1	23415	70468;70469;70470	chr2:178542791;178542790;178542789	chr2:179407518;179407517;179407516
Novex-2	23482	70669;70670;70671	chr2:178542791;178542790;178542789	chr2:179407518;179407517;179407516
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: Ig-154
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.26
• 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/G	None	None	0.492	N	0.56	0.53	0.786383566872	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1727	likely_benign	0.138	benign	-1.341	Destabilizing	0.165	N	0.332	neutral	N	0.520383822	None	None	N
V/C	0.7004	likely_pathogenic	0.6145	pathogenic	-1.002	Destabilizing	0.981	D	0.541	neutral	None	None	None	None	N
V/D	0.7083	likely_pathogenic	0.6144	pathogenic	-0.905	Destabilizing	0.912	D	0.606	neutral	N	0.510529578	None	None	N
V/E	0.5046	ambiguous	0.4251	ambiguous	-0.892	Destabilizing	0.818	D	0.577	neutral	None	None	None	None	N
V/F	0.1512	likely_benign	0.1293	benign	-0.976	Destabilizing	0.001	N	0.328	neutral	N	0.479883994	None	None	N
V/G	0.2915	likely_benign	0.2312	benign	-1.674	Destabilizing	0.492	N	0.56	neutral	N	0.491918344	None	None	N
V/H	0.677	likely_pathogenic	0.575	pathogenic	-1.146	Destabilizing	0.981	D	0.593	neutral	None	None	None	None	N
V/I	0.0747	likely_benign	0.0714	benign	-0.531	Destabilizing	None	N	0.089	neutral	N	0.432935409	None	None	N
V/K	0.5169	ambiguous	0.4308	ambiguous	-1.058	Destabilizing	0.69	D	0.575	neutral	None	None	None	None	N
V/L	0.1657	likely_benign	0.1335	benign	-0.531	Destabilizing	0.006	N	0.28	neutral	N	0.502566066	None	None	N
V/M	0.1078	likely_benign	0.0928	benign	-0.491	Destabilizing	0.054	N	0.263	neutral	None	None	None	None	N
V/N	0.4825	ambiguous	0.3915	ambiguous	-0.879	Destabilizing	0.932	D	0.611	neutral	None	None	None	None	N
V/P	0.7681	likely_pathogenic	0.6898	pathogenic	-0.765	Destabilizing	0.932	D	0.585	neutral	None	None	None	None	N
V/Q	0.4565	ambiguous	0.3768	ambiguous	-1.009	Destabilizing	0.818	D	0.586	neutral	None	None	None	None	N
V/R	0.4319	ambiguous	0.3437	ambiguous	-0.595	Destabilizing	0.818	D	0.612	neutral	None	None	None	None	N
V/S	0.2561	likely_benign	0.2069	benign	-1.463	Destabilizing	0.563	D	0.524	neutral	None	None	None	None	N
V/T	0.1627	likely_benign	0.1347	benign	-1.328	Destabilizing	0.388	N	0.403	neutral	None	None	None	None	N
V/W	0.7082	likely_pathogenic	0.6214	pathogenic	-1.149	Destabilizing	0.944	D	0.603	neutral	None	None	None	None	N
V/Y	0.5362	ambiguous	0.4509	ambiguous	-0.842	Destabilizing	0.241	N	0.553	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.