TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35184	105775;105776;105777	chr2:178531065;178531064;178531063	chr2:179395792;179395791;179395790
N2AB	33543	100852;100853;100854	chr2:178531065;178531064;178531063	chr2:179395792;179395791;179395790
N2A	32616	98071;98072;98073	chr2:178531065;178531064;178531063	chr2:179395792;179395791;179395790
N2B	26119	78580;78581;78582	chr2:178531065;178531064;178531063	chr2:179395792;179395791;179395790
Novex-1	26244	78955;78956;78957	chr2:178531065;178531064;178531063	chr2:179395792;179395791;179395790
Novex-2	26311	79156;79157;79158	chr2:178531065;178531064;178531063	chr2:179395792;179395791;179395790
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-164
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0912
• 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
S/A	None	None	0.992	N	0.597	0.306	0.186928172975	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02334E-05

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
S/A	0.2285	likely_benign	0.2092	benign	-0.669	Destabilizing	0.992	D	0.597	neutral	N	0.451551057	None	None	N
S/C	0.3599	ambiguous	0.3405	ambiguous	-0.983	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
S/D	0.9637	likely_pathogenic	0.9692	pathogenic	-2.025	Highly Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
S/E	0.9797	likely_pathogenic	0.982	pathogenic	-1.878	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
S/F	0.9274	likely_pathogenic	0.9383	pathogenic	-0.929	Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
S/G	0.4101	ambiguous	0.4048	ambiguous	-0.976	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
S/H	0.9133	likely_pathogenic	0.9259	pathogenic	-1.477	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
S/I	0.8554	likely_pathogenic	0.8569	pathogenic	0.078	Stabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
S/K	0.9955	likely_pathogenic	0.9961	pathogenic	-0.37	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
S/L	0.689	likely_pathogenic	0.6686	pathogenic	0.078	Stabilizing	0.999	D	0.789	deleterious	N	0.474694969	None	None	N
S/M	0.7647	likely_pathogenic	0.7557	pathogenic	0.078	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
S/N	0.7439	likely_pathogenic	0.7485	pathogenic	-1.15	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
S/P	0.9917	likely_pathogenic	0.9933	pathogenic	-0.139	Destabilizing	0.999	D	0.856	deleterious	N	0.47401386	None	None	N
S/Q	0.9648	likely_pathogenic	0.9687	pathogenic	-1.077	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
S/R	0.9922	likely_pathogenic	0.9934	pathogenic	-0.569	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
S/T	0.2314	likely_benign	0.208	benign	-0.75	Destabilizing	0.997	D	0.613	neutral	N	0.451728868	None	None	N
S/V	0.7618	likely_pathogenic	0.7518	pathogenic	-0.139	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
S/W	0.9407	likely_pathogenic	0.9581	pathogenic	-1.217	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
S/Y	0.842	likely_pathogenic	0.869	pathogenic	-0.723	Destabilizing	0.999	D	0.878	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.