TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20555	61888;61889;61890	chr2:178590062;178590061;178590060	chr2:179454789;179454788;179454787
N2AB	18914	56965;56966;56967	chr2:178590062;178590061;178590060	chr2:179454789;179454788;179454787
N2A	17987	54184;54185;54186	chr2:178590062;178590061;178590060	chr2:179454789;179454788;179454787
N2B	11490	34693;34694;34695	chr2:178590062;178590061;178590060	chr2:179454789;179454788;179454787
Novex-1	11615	35068;35069;35070	chr2:178590062;178590061;178590060	chr2:179454789;179454788;179454787
Novex-2	11682	35269;35270;35271	chr2:178590062;178590061;178590060	chr2:179454789;179454788;179454787
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-121
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.7472
• 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/N	rs1559577387	None	0.492	N	0.429	0.235	0.259761712551	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.0707	likely_benign	0.0789	benign	-0.29	Destabilizing	0.004	N	0.223	neutral	None	None	None	None	I
S/C	0.0657	likely_benign	0.0693	benign	-0.418	Destabilizing	0.001	N	0.313	neutral	N	0.479187774	None	None	I
S/D	0.7902	likely_pathogenic	0.8924	pathogenic	-0.174	Destabilizing	0.563	D	0.391	neutral	None	None	None	None	I
S/E	0.8358	likely_pathogenic	0.9049	pathogenic	-0.283	Destabilizing	0.563	D	0.415	neutral	None	None	None	None	I
S/F	0.324	likely_benign	0.4723	ambiguous	-1.058	Destabilizing	0.818	D	0.601	neutral	None	None	None	None	I
S/G	0.1102	likely_benign	0.1408	benign	-0.288	Destabilizing	None	N	0.226	neutral	N	0.459484505	None	None	I
S/H	0.6114	likely_pathogenic	0.7133	pathogenic	-0.613	Destabilizing	0.981	D	0.542	neutral	None	None	None	None	I
S/I	0.2668	likely_benign	0.3666	ambiguous	-0.411	Destabilizing	0.627	D	0.581	neutral	N	0.464698324	None	None	I
S/K	0.9165	likely_pathogenic	0.9593	pathogenic	-0.409	Destabilizing	0.388	N	0.389	neutral	None	None	None	None	I
S/L	0.1458	likely_benign	0.2161	benign	-0.411	Destabilizing	0.241	N	0.562	neutral	None	None	None	None	I
S/M	0.2922	likely_benign	0.3628	ambiguous	-0.266	Destabilizing	0.932	D	0.539	neutral	None	None	None	None	I
S/N	0.3394	likely_benign	0.4663	ambiguous	-0.195	Destabilizing	0.492	N	0.429	neutral	N	0.501909918	None	None	I
S/P	0.8296	likely_pathogenic	0.9256	pathogenic	-0.353	Destabilizing	0.818	D	0.509	neutral	None	None	None	None	I
S/Q	0.7567	likely_pathogenic	0.8308	pathogenic	-0.406	Destabilizing	0.932	D	0.423	neutral	None	None	None	None	I
S/R	0.8238	likely_pathogenic	0.9059	pathogenic	-0.218	Destabilizing	0.773	D	0.513	neutral	N	0.487999258	None	None	I
S/T	0.1208	likely_benign	0.1565	benign	-0.316	Destabilizing	0.324	N	0.397	neutral	N	0.503061924	None	None	I
S/V	0.2174	likely_benign	0.2822	benign	-0.353	Destabilizing	0.241	N	0.559	neutral	None	None	None	None	I
S/W	0.6112	likely_pathogenic	0.7326	pathogenic	-1.144	Destabilizing	0.981	D	0.599	neutral	None	None	None	None	I
S/Y	0.364	ambiguous	0.5025	ambiguous	-0.849	Destabilizing	0.932	D	0.599	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.