TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18260	55003;55004;55005	chr2:178603909;178603908;178603907	chr2:179468636;179468635;179468634
N2AB	16619	50080;50081;50082	chr2:178603909;178603908;178603907	chr2:179468636;179468635;179468634
N2A	15692	47299;47300;47301	chr2:178603909;178603908;178603907	chr2:179468636;179468635;179468634
N2B	9195	27808;27809;27810	chr2:178603909;178603908;178603907	chr2:179468636;179468635;179468634
Novex-1	9320	28183;28184;28185	chr2:178603909;178603908;178603907	chr2:179468636;179468635;179468634
Novex-2	9387	28384;28385;28386	chr2:178603909;178603908;178603907	chr2:179468636;179468635;179468634
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-20
• Domain position: 95
• Structural Position: 123
• Q(SASA): 0.416
• 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
P/T	None	None	0.986	N	0.643	0.271	0.355242300401	gnomAD-4.0.0	1.59858E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87467E-06	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
P/A	0.0742	likely_benign	0.0637	benign	-1.728	Destabilizing	0.214	N	0.303	neutral	N	0.47980577	None	None	N
P/C	0.5529	ambiguous	0.4954	ambiguous	-1.066	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/D	0.7028	likely_pathogenic	0.6457	pathogenic	-1.547	Destabilizing	0.995	D	0.595	neutral	None	None	None	None	N
P/E	0.441	ambiguous	0.3733	ambiguous	-1.509	Destabilizing	0.995	D	0.561	neutral	None	None	None	None	N
P/F	0.6918	likely_pathogenic	0.5735	pathogenic	-1.29	Destabilizing	0.995	D	0.8	deleterious	None	None	None	None	N
P/G	0.4953	ambiguous	0.3969	ambiguous	-2.09	Highly Destabilizing	0.964	D	0.645	neutral	None	None	None	None	N
P/H	0.5622	ambiguous	0.4819	ambiguous	-1.569	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
P/I	0.2791	likely_benign	0.1998	benign	-0.81	Destabilizing	0.455	N	0.539	neutral	None	None	None	None	N
P/K	0.6696	likely_pathogenic	0.618	pathogenic	-1.238	Destabilizing	0.995	D	0.547	neutral	None	None	None	None	N
P/L	0.1913	likely_benign	0.1484	benign	-0.81	Destabilizing	0.91	D	0.675	prob.neutral	N	0.46987062	None	None	N
P/M	0.3774	ambiguous	0.3019	benign	-0.606	Destabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
P/N	0.627	likely_pathogenic	0.5492	ambiguous	-1.081	Destabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
P/Q	0.4098	ambiguous	0.3491	ambiguous	-1.228	Destabilizing	0.998	D	0.596	neutral	N	0.499143824	None	None	N
P/R	0.5674	likely_pathogenic	0.4911	ambiguous	-0.744	Destabilizing	0.993	D	0.729	deleterious	N	0.51024664	None	None	N
P/S	0.2188	likely_benign	0.1764	benign	-1.668	Destabilizing	0.91	D	0.607	neutral	N	0.519748238	None	None	N
P/T	0.1554	likely_benign	0.1303	benign	-1.516	Destabilizing	0.986	D	0.643	neutral	N	0.511859474	None	None	N
P/V	0.1821	likely_benign	0.1371	benign	-1.083	Destabilizing	0.931	D	0.584	neutral	None	None	None	None	N
P/W	0.8754	likely_pathogenic	0.808	pathogenic	-1.507	Destabilizing	1.0	D	0.705	prob.delet.	None	None	None	None	N
P/Y	0.7205	likely_pathogenic	0.6279	pathogenic	-1.209	Destabilizing	0.998	D	0.781	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.