TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7898	23917;23918;23919	chr2:178719800;178719799;178719798	chr2:179584527;179584526;179584525
N2AB	7581	22966;22967;22968	chr2:178719800;178719799;178719798	chr2:179584527;179584526;179584525
N2A	6654	20185;20186;20187	chr2:178719800;178719799;178719798	chr2:179584527;179584526;179584525
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: 10
• Structural Position: 13
• Q(SASA): 0.1616
• 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
M/I	rs751897366	-0.435	0.001	N	0.057	0.139	0.339793275041	gnomAD-2.1.1	6.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	4.90966E-04	None	0	0	0
M/I	rs751897366	-0.435	0.001	N	0.057	0.139	0.339793275041	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	8.28157E-04	0
M/I	rs751897366	-0.435	0.001	N	0.057	0.139	0.339793275041	gnomAD-4.0.0	6.84579E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99938E-07	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
M/A	0.3608	ambiguous	0.3971	ambiguous	-2.101	Highly Destabilizing	0.176	N	0.245	neutral	None	None	None	None	N
M/C	0.782	likely_pathogenic	0.8099	pathogenic	-1.628	Destabilizing	0.981	D	0.459	neutral	None	None	None	None	N
M/D	0.8985	likely_pathogenic	0.9234	pathogenic	-0.941	Destabilizing	0.704	D	0.615	neutral	None	None	None	None	N
M/E	0.5453	ambiguous	0.6007	pathogenic	-0.823	Destabilizing	0.704	D	0.537	neutral	None	None	None	None	N
M/F	0.4022	ambiguous	0.3914	ambiguous	-0.782	Destabilizing	0.704	D	0.317	neutral	None	None	None	None	N
M/G	0.6685	likely_pathogenic	0.7121	pathogenic	-2.501	Highly Destabilizing	0.704	D	0.515	neutral	None	None	None	None	N
M/H	0.6439	likely_pathogenic	0.7078	pathogenic	-1.599	Destabilizing	0.981	D	0.515	neutral	None	None	None	None	N
M/I	0.2602	likely_benign	0.3002	benign	-1.011	Destabilizing	0.001	N	0.057	neutral	N	0.399396052	None	None	N
M/K	0.2644	likely_benign	0.3138	benign	-1.004	Destabilizing	0.642	D	0.459	neutral	N	0.485246955	None	None	N
M/L	0.127	likely_benign	0.1515	benign	-1.011	Destabilizing	0.001	N	0.042	neutral	N	0.419616608	None	None	N
M/N	0.668	likely_pathogenic	0.727	pathogenic	-1.061	Destabilizing	0.704	D	0.59	neutral	None	None	None	None	N
M/P	0.9472	likely_pathogenic	0.9591	pathogenic	-1.35	Destabilizing	0.828	D	0.59	neutral	None	None	None	None	N
M/Q	0.2887	likely_benign	0.317	benign	-0.974	Destabilizing	0.828	D	0.431	neutral	None	None	None	None	N
M/R	0.2698	likely_benign	0.3224	benign	-0.68	Destabilizing	0.784	D	0.525	neutral	N	0.472760447	None	None	N
M/S	0.4973	ambiguous	0.5334	ambiguous	-1.71	Destabilizing	0.329	N	0.385	neutral	None	None	None	None	N
M/T	0.2008	likely_benign	0.2236	benign	-1.465	Destabilizing	0.003	N	0.135	neutral	N	0.435799569	None	None	N
M/V	0.075	likely_benign	0.0841	benign	-1.35	Destabilizing	0.065	N	0.223	neutral	N	0.381479508	None	None	N
M/W	0.7653	likely_pathogenic	0.8041	pathogenic	-0.811	Destabilizing	0.995	D	0.427	neutral	None	None	None	None	N
M/Y	0.705	likely_pathogenic	0.7415	pathogenic	-0.862	Destabilizing	0.981	D	0.565	neutral	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.