TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6210	18853;18854;18855	chr2:178729528;178729527;178729526	chr2:179594255;179594254;179594253
N2AB	5893	17902;17903;17904	chr2:178729528;178729527;178729526	chr2:179594255;179594254;179594253
N2A	4966	15121;15122;15123	chr2:178729528;178729527;178729526	chr2:179594255;179594254;179594253
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-46
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1852
• 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	rs766360972	-0.56	0.63	N	0.491	0.265	0.61403422888	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24059E-04	0	None	0	0	None	0	None	0	0	0
V/I	rs766360972	-0.56	0.63	N	0.491	0.265	0.61403422888	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20639E-04	0	0	0	0	None	0	0	0	0	0
V/I	rs766360972	-0.56	0.63	N	0.491	0.265	0.61403422888	gnomAD-4.0.0	6.08971E-06	None	None	None	None	N	None	1.04836E-04	0	None	0	0	None	0	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	0.1559	likely_benign	0.1448	benign	-1.685	Destabilizing	0.025	N	0.266	neutral	D	0.532984973	None	None	N
V/C	0.8557	likely_pathogenic	0.8411	pathogenic	-1.243	Destabilizing	0.997	D	0.567	neutral	None	None	None	None	N
V/D	0.7043	likely_pathogenic	0.5889	pathogenic	-1.553	Destabilizing	0.987	D	0.677	prob.neutral	None	None	None	None	N
V/E	0.6421	likely_pathogenic	0.5301	ambiguous	-1.526	Destabilizing	0.967	D	0.619	neutral	D	0.541270812	None	None	N
V/F	0.3255	likely_benign	0.2944	benign	-1.257	Destabilizing	0.975	D	0.635	neutral	None	None	None	None	N
V/G	0.2883	likely_benign	0.2439	benign	-2.039	Highly Destabilizing	0.935	D	0.647	neutral	D	0.527027671	None	None	N
V/H	0.8685	likely_pathogenic	0.8127	pathogenic	-1.578	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
V/I	0.0993	likely_benign	0.0986	benign	-0.793	Destabilizing	0.63	D	0.491	neutral	N	0.487826512	None	None	N
V/K	0.7323	likely_pathogenic	0.6119	pathogenic	-1.378	Destabilizing	0.975	D	0.62	neutral	None	None	None	None	N
V/L	0.3975	ambiguous	0.3671	ambiguous	-0.793	Destabilizing	0.025	N	0.255	neutral	N	0.491157875	None	None	N
V/M	0.2447	likely_benign	0.2128	benign	-0.662	Destabilizing	0.975	D	0.552	neutral	None	None	None	None	N
V/N	0.5723	likely_pathogenic	0.482	ambiguous	-1.21	Destabilizing	0.987	D	0.683	prob.neutral	None	None	None	None	N
V/P	0.9009	likely_pathogenic	0.8528	pathogenic	-1.057	Destabilizing	0.987	D	0.629	neutral	None	None	None	None	N
V/Q	0.6987	likely_pathogenic	0.607	pathogenic	-1.356	Destabilizing	0.987	D	0.629	neutral	None	None	None	None	N
V/R	0.6793	likely_pathogenic	0.5673	pathogenic	-0.901	Destabilizing	0.987	D	0.68	prob.neutral	None	None	None	None	N
V/S	0.3534	ambiguous	0.2967	benign	-1.786	Destabilizing	0.95	D	0.611	neutral	None	None	None	None	N
V/T	0.1733	likely_benign	0.1666	benign	-1.646	Destabilizing	0.916	D	0.531	neutral	None	None	None	None	N
V/W	0.9333	likely_pathogenic	0.9089	pathogenic	-1.463	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
V/Y	0.7834	likely_pathogenic	0.7298	pathogenic	-1.173	Destabilizing	0.996	D	0.614	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.