TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26025	78298;78299;78300	chr2:178568059;178568058;178568057	chr2:179432786;179432785;179432784
N2AB	24384	73375;73376;73377	chr2:178568059;178568058;178568057	chr2:179432786;179432785;179432784
N2A	23457	70594;70595;70596	chr2:178568059;178568058;178568057	chr2:179432786;179432785;179432784
N2B	16960	51103;51104;51105	chr2:178568059;178568058;178568057	chr2:179432786;179432785;179432784
Novex-1	17085	51478;51479;51480	chr2:178568059;178568058;178568057	chr2:179432786;179432785;179432784
Novex-2	17152	51679;51680;51681	chr2:178568059;178568058;178568057	chr2:179432786;179432785;179432784
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-77
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0924
• 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
Y/D	rs759173173	-4.041	1.0	D	0.942	0.872	0.915270232398	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
Y/D	rs759173173	-4.041	1.0	D	0.942	0.872	0.915270232398	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	2.77901E-05	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
Y/A	0.9987	likely_pathogenic	0.9992	pathogenic	-3.941	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/C	0.9297	likely_pathogenic	0.9494	pathogenic	-2.332	Highly Destabilizing	1.0	D	0.921	deleterious	D	0.665120915	None	None	N
Y/D	0.999	likely_pathogenic	0.9994	pathogenic	-3.863	Highly Destabilizing	1.0	D	0.942	deleterious	D	0.665322719	None	None	N
Y/E	0.9997	likely_pathogenic	0.9998	pathogenic	-3.686	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
Y/F	0.2134	likely_benign	0.2266	benign	-1.825	Destabilizing	0.999	D	0.641	neutral	D	0.586933224	None	None	N
Y/G	0.9953	likely_pathogenic	0.9968	pathogenic	-4.261	Highly Destabilizing	1.0	D	0.946	deleterious	None	None	None	None	N
Y/H	0.9829	likely_pathogenic	0.9871	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.664717306	None	None	N
Y/I	0.9873	likely_pathogenic	0.9907	pathogenic	-2.818	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/K	0.9991	likely_pathogenic	0.9994	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
Y/L	0.9761	likely_pathogenic	0.9816	pathogenic	-2.818	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
Y/M	0.9921	likely_pathogenic	0.9939	pathogenic	-2.478	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/N	0.9879	likely_pathogenic	0.992	pathogenic	-3.505	Highly Destabilizing	1.0	D	0.935	deleterious	D	0.665120915	None	None	N
Y/P	0.9998	likely_pathogenic	0.9999	pathogenic	-3.213	Highly Destabilizing	1.0	D	0.959	deleterious	None	None	None	None	N
Y/Q	0.9991	likely_pathogenic	0.9994	pathogenic	-3.325	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/R	0.9962	likely_pathogenic	0.9973	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
Y/S	0.9936	likely_pathogenic	0.996	pathogenic	-3.82	Highly Destabilizing	1.0	D	0.935	deleterious	D	0.665120915	None	None	N
Y/T	0.9983	likely_pathogenic	0.999	pathogenic	-3.556	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
Y/V	0.9804	likely_pathogenic	0.9855	pathogenic	-3.213	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/W	0.8553	likely_pathogenic	0.8582	pathogenic	-1.054	Destabilizing	1.0	D	0.797	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.