TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23214	69865;69866;69867	chr2:178576604;178576603;178576602	chr2:179441331;179441330;179441329
N2AB	21573	64942;64943;64944	chr2:178576604;178576603;178576602	chr2:179441331;179441330;179441329
N2A	20646	62161;62162;62163	chr2:178576604;178576603;178576602	chr2:179441331;179441330;179441329
N2B	14149	42670;42671;42672	chr2:178576604;178576603;178576602	chr2:179441331;179441330;179441329
Novex-1	14274	43045;43046;43047	chr2:178576604;178576603;178576602	chr2:179441331;179441330;179441329
Novex-2	14341	43246;43247;43248	chr2:178576604;178576603;178576602	chr2:179441331;179441330;179441329
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-56
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.1235
• 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	rs1213856899	-0.631	0.997	D	0.626	0.403	0.756004659829	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
V/I	rs1213856899	-0.631	0.997	D	0.626	0.403	0.756004659829	gnomAD-4.0.0	1.20032E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-05	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	0.6518	likely_pathogenic	0.6467	pathogenic	-2.425	Highly Destabilizing	0.999	D	0.698	prob.neutral	D	0.545896076	None	None	N
V/C	0.9429	likely_pathogenic	0.9442	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9981	pathogenic	-3.445	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.644110039	None	None	N
V/E	0.9944	likely_pathogenic	0.995	pathogenic	-3.18	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/F	0.9319	likely_pathogenic	0.9319	pathogenic	-1.247	Destabilizing	1.0	D	0.787	deleterious	D	0.566633677	None	None	N
V/G	0.895	likely_pathogenic	0.9087	pathogenic	-2.975	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.644110039	None	None	N
V/H	0.9985	likely_pathogenic	0.9986	pathogenic	-2.713	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/I	0.1345	likely_benign	0.1234	benign	-0.844	Destabilizing	0.997	D	0.626	neutral	D	0.523424128	None	None	N
V/K	0.9972	likely_pathogenic	0.9975	pathogenic	-1.97	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/L	0.7911	likely_pathogenic	0.7734	pathogenic	-0.844	Destabilizing	0.997	D	0.715	prob.delet.	N	0.515506782	None	None	N
V/M	0.8611	likely_pathogenic	0.8531	pathogenic	-1.269	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/N	0.9913	likely_pathogenic	0.9921	pathogenic	-2.505	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/P	0.9955	likely_pathogenic	0.9954	pathogenic	-1.351	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/Q	0.9935	likely_pathogenic	0.9943	pathogenic	-2.248	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/R	0.9911	likely_pathogenic	0.9928	pathogenic	-1.895	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/S	0.9303	likely_pathogenic	0.9318	pathogenic	-3.035	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/T	0.8737	likely_pathogenic	0.8771	pathogenic	-2.63	Highly Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9993	pathogenic	-1.818	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/Y	0.9939	likely_pathogenic	0.9943	pathogenic	-1.54	Destabilizing	1.0	D	0.789	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.