TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7953	24082;24083;24084	chr2:178719635;178719634;178719633	chr2:179584362;179584361;179584360
N2AB	7636	23131;23132;23133	chr2:178719635;178719634;178719633	chr2:179584362;179584361;179584360
N2A	6709	20350;20351;20352	chr2:178719635;178719634;178719633	chr2:179584362;179584361;179584360
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-64
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.6983
• 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
M/I	rs1218890532	0.543	0.784	N	0.18	0.144	0.301455362545	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.65837E-04
M/I	rs1218890532	0.543	0.784	N	0.18	0.144	0.301455362545	gnomAD-4.0.0	1.36846E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.31334E-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
M/A	0.1824	likely_benign	0.1886	benign	-0.561	Destabilizing	0.3	N	0.189	neutral	None	None	None	None	I
M/C	0.6694	likely_pathogenic	0.6878	pathogenic	-0.382	Destabilizing	0.981	D	0.215	neutral	None	None	None	None	I
M/D	0.4522	ambiguous	0.4614	ambiguous	0.263	Stabilizing	0.329	N	0.276	neutral	None	None	None	None	I
M/E	0.2255	likely_benign	0.2392	benign	0.205	Stabilizing	0.329	N	0.178	neutral	None	None	None	None	I
M/F	0.2378	likely_benign	0.2483	benign	-0.242	Destabilizing	0.981	D	0.227	neutral	None	None	None	None	I
M/G	0.3307	likely_benign	0.3524	ambiguous	-0.739	Destabilizing	0.495	N	0.192	neutral	None	None	None	None	I
M/H	0.3119	likely_benign	0.331	benign	0.061	Stabilizing	0.944	D	0.26	neutral	None	None	None	None	I
M/I	0.1576	likely_benign	0.1579	benign	-0.187	Destabilizing	0.784	D	0.18	neutral	N	0.419170238	None	None	I
M/K	0.0928	likely_benign	0.1009	benign	0.379	Stabilizing	0.001	N	0.105	neutral	N	0.343325685	None	None	I
M/L	0.0954	likely_benign	0.0985	benign	-0.187	Destabilizing	0.244	N	0.135	neutral	N	0.361140655	None	None	I
M/N	0.2158	likely_benign	0.2143	benign	0.571	Stabilizing	0.013	N	0.107	neutral	None	None	None	None	I
M/P	0.2184	likely_benign	0.224	benign	-0.283	Destabilizing	0.828	D	0.357	neutral	None	None	None	None	I
M/Q	0.1499	likely_benign	0.16	benign	0.382	Stabilizing	0.704	D	0.145	neutral	None	None	None	None	I
M/R	0.1035	likely_benign	0.1095	benign	0.882	Stabilizing	0.001	N	0.093	neutral	N	0.388519257	None	None	I
M/S	0.221	likely_benign	0.2306	benign	0.101	Stabilizing	0.495	N	0.182	neutral	None	None	None	None	I
M/T	0.1307	likely_benign	0.1374	benign	0.144	Stabilizing	0.425	N	0.24	neutral	N	0.409742678	None	None	I
M/V	0.0764	likely_benign	0.0766	benign	-0.283	Destabilizing	0.6	D	0.162	neutral	N	0.399082968	None	None	I
M/W	0.4673	ambiguous	0.5024	ambiguous	-0.2	Destabilizing	0.995	D	0.221	neutral	None	None	None	None	I
M/Y	0.3618	ambiguous	0.3824	ambiguous	-0.057	Destabilizing	0.981	D	0.291	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.