TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31920	95983;95984;95985	chr2:178544471;178544470;178544469	chr2:179409198;179409197;179409196
N2AB	30279	91060;91061;91062	chr2:178544471;178544470;178544469	chr2:179409198;179409197;179409196
N2A	29352	88279;88280;88281	chr2:178544471;178544470;178544469	chr2:179409198;179409197;179409196
N2B	22855	68788;68789;68790	chr2:178544471;178544470;178544469	chr2:179409198;179409197;179409196
Novex-1	22980	69163;69164;69165	chr2:178544471;178544470;178544469	chr2:179409198;179409197;179409196
Novex-2	23047	69364;69365;69366	chr2:178544471;178544470;178544469	chr2:179409198;179409197;179409196
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-121
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4814
• 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
D/G	None	None	1.0	N	0.706	0.472	0.346768085243	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	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
D/A	0.8281	likely_pathogenic	0.8336	pathogenic	-0.508	Destabilizing	1.0	D	0.691	prob.neutral	N	0.514035774	None	None	N
D/C	0.9822	likely_pathogenic	0.9829	pathogenic	0.051	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
D/E	0.7969	likely_pathogenic	0.8039	pathogenic	-0.435	Destabilizing	1.0	D	0.384	neutral	N	0.485521021	None	None	N
D/F	0.9791	likely_pathogenic	0.9767	pathogenic	-0.522	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
D/G	0.7461	likely_pathogenic	0.7832	pathogenic	-0.727	Destabilizing	1.0	D	0.706	prob.neutral	N	0.519577667	None	None	N
D/H	0.9381	likely_pathogenic	0.9315	pathogenic	-0.636	Destabilizing	1.0	D	0.609	neutral	N	0.491843351	None	None	N
D/I	0.9827	likely_pathogenic	0.977	pathogenic	0.028	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
D/K	0.9699	likely_pathogenic	0.9674	pathogenic	0.187	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
D/L	0.9616	likely_pathogenic	0.9567	pathogenic	0.028	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
D/M	0.9884	likely_pathogenic	0.9866	pathogenic	0.383	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
D/N	0.4617	ambiguous	0.4889	ambiguous	-0.106	Destabilizing	1.0	D	0.626	neutral	N	0.50614701	None	None	N
D/P	0.998	likely_pathogenic	0.9974	pathogenic	-0.129	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
D/Q	0.9583	likely_pathogenic	0.9534	pathogenic	-0.086	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
D/R	0.9641	likely_pathogenic	0.9591	pathogenic	0.219	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
D/S	0.6528	likely_pathogenic	0.6699	pathogenic	-0.235	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
D/T	0.9208	likely_pathogenic	0.9109	pathogenic	-0.063	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/V	0.9454	likely_pathogenic	0.929	pathogenic	-0.129	Destabilizing	1.0	D	0.722	prob.delet.	N	0.493044665	None	None	N
D/W	0.9965	likely_pathogenic	0.9955	pathogenic	-0.381	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
D/Y	0.8763	likely_pathogenic	0.8582	pathogenic	-0.285	Destabilizing	1.0	D	0.626	neutral	N	0.494312113	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.