TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28202	84829;84830;84831	chr2:178561528;178561527;178561526	chr2:179426255;179426254;179426253
N2AB	26561	79906;79907;79908	chr2:178561528;178561527;178561526	chr2:179426255;179426254;179426253
N2A	25634	77125;77126;77127	chr2:178561528;178561527;178561526	chr2:179426255;179426254;179426253
N2B	19137	57634;57635;57636	chr2:178561528;178561527;178561526	chr2:179426255;179426254;179426253
Novex-1	19262	58009;58010;58011	chr2:178561528;178561527;178561526	chr2:179426255;179426254;179426253
Novex-2	19329	58210;58211;58212	chr2:178561528;178561527;178561526	chr2:179426255;179426254;179426253
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: Fn3-93
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.2212
• Predicted PPI site: I

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/P	None	None	0.301	N	0.329	0.142	0.152612264143	gnomAD-4.0.0	1.5923E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02535E-05
S/T	rs747544266	-0.057	None	N	0.125	0.123	0.0551355673512	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.66E-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
S/A	0.0796	likely_benign	0.079	benign	-0.492	Destabilizing	None	N	0.126	neutral	N	0.43892194	None	None	I
S/C	0.0782	likely_benign	0.0791	benign	-0.355	Destabilizing	0.667	D	0.355	neutral	None	None	None	None	I
S/D	0.4703	ambiguous	0.4714	ambiguous	0.489	Stabilizing	0.22	N	0.267	neutral	None	None	None	None	I
S/E	0.4565	ambiguous	0.4501	ambiguous	0.482	Stabilizing	0.104	N	0.259	neutral	None	None	None	None	I
S/F	0.1951	likely_benign	0.1929	benign	-0.731	Destabilizing	0.497	N	0.423	neutral	None	None	None	None	I
S/G	0.0978	likely_benign	0.0954	benign	-0.712	Destabilizing	0.055	N	0.27	neutral	None	None	None	None	I
S/H	0.2299	likely_benign	0.224	benign	-0.981	Destabilizing	0.001	N	0.249	neutral	None	None	None	None	I
S/I	0.1294	likely_benign	0.1229	benign	-0.021	Destabilizing	0.055	N	0.331	neutral	None	None	None	None	I
S/K	0.4735	ambiguous	0.4404	ambiguous	-0.322	Destabilizing	0.104	N	0.272	neutral	None	None	None	None	I
S/L	0.085	likely_benign	0.0836	benign	-0.021	Destabilizing	0.042	N	0.317	neutral	N	0.434652271	None	None	I
S/M	0.1223	likely_benign	0.1237	benign	-0.067	Destabilizing	0.667	D	0.359	neutral	None	None	None	None	I
S/N	0.0921	likely_benign	0.0919	benign	-0.286	Destabilizing	0.22	N	0.281	neutral	None	None	None	None	I
S/P	0.8525	likely_pathogenic	0.8462	pathogenic	-0.145	Destabilizing	0.301	N	0.329	neutral	N	0.489292045	None	None	I
S/Q	0.3173	likely_benign	0.3024	benign	-0.365	Destabilizing	0.364	N	0.321	neutral	None	None	None	None	I
S/R	0.4374	ambiguous	0.3962	ambiguous	-0.222	Destabilizing	0.22	N	0.347	neutral	None	None	None	None	I
S/T	0.0623	likely_benign	0.0617	benign	-0.365	Destabilizing	None	N	0.125	neutral	N	0.33876052	None	None	I
S/V	0.1205	likely_benign	0.1152	benign	-0.145	Destabilizing	None	N	0.209	neutral	None	None	None	None	I
S/W	0.3415	ambiguous	0.3311	benign	-0.745	Destabilizing	0.958	D	0.408	neutral	None	None	None	None	I
S/Y	0.1644	likely_benign	0.1595	benign	-0.44	Destabilizing	0.22	N	0.421	neutral	None	None	None	None	I

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.