TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6448	19567;19568;19569	chr2:178728584;178728583;178728582	chr2:179593311;179593310;179593309
N2AB	6131	18616;18617;18618	chr2:178728584;178728583;178728582	chr2:179593311;179593310;179593309
N2A	5204	15835;15836;15837	chr2:178728584;178728583;178728582	chr2:179593311;179593310;179593309
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-48
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.3152
• 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	None	None	0.468	N	0.173	0.114	0.429203605099	gnomAD-4.0.0	1.59276E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43365E-05	0
M/V	rs1305903315	None	0.159	N	0.177	0.084	0.408172294925	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
M/V	rs1305903315	None	0.159	N	0.177	0.084	0.408172294925	gnomAD-4.0.0	6.81902E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.3255E-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
M/A	0.2304	likely_benign	0.2531	benign	-1.474	Destabilizing	0.051	N	0.193	neutral	None	None	None	None	N
M/C	0.689	likely_pathogenic	0.734	pathogenic	-1.149	Destabilizing	0.968	D	0.341	neutral	None	None	None	None	N
M/D	0.501	ambiguous	0.5602	ambiguous	-0.219	Destabilizing	0.001	N	0.137	neutral	None	None	None	None	N
M/E	0.213	likely_benign	0.2465	benign	-0.171	Destabilizing	0.003	N	0.099	neutral	None	None	None	None	N
M/F	0.3161	likely_benign	0.3375	benign	-0.451	Destabilizing	0.896	D	0.201	neutral	None	None	None	None	N
M/G	0.3012	likely_benign	0.3816	ambiguous	-1.791	Destabilizing	0.111	N	0.261	neutral	None	None	None	None	N
M/H	0.3535	ambiguous	0.3907	ambiguous	-0.721	Destabilizing	0.908	D	0.467	neutral	None	None	None	None	N
M/I	0.3561	ambiguous	0.3311	benign	-0.66	Destabilizing	0.468	N	0.173	neutral	N	0.451595741	None	None	N
M/K	0.1028	likely_benign	0.1164	benign	-0.399	Destabilizing	0.086	N	0.231	neutral	N	0.391083213	None	None	N
M/L	0.1074	likely_benign	0.1054	benign	-0.66	Destabilizing	0.076	N	0.189	neutral	N	0.425563933	None	None	N
M/N	0.2367	likely_benign	0.2722	benign	-0.38	Destabilizing	0.2	N	0.326	neutral	None	None	None	None	N
M/P	0.8062	likely_pathogenic	0.831	pathogenic	-0.905	Destabilizing	0.538	D	0.341	neutral	None	None	None	None	N
M/Q	0.1065	likely_benign	0.1319	benign	-0.401	Destabilizing	0.008	N	0.091	neutral	None	None	None	None	N
M/R	0.1122	likely_benign	0.1252	benign	0.069	Stabilizing	0.302	N	0.348	neutral	N	0.392643438	None	None	N
M/S	0.1712	likely_benign	0.2028	benign	-0.999	Destabilizing	0.003	N	0.101	neutral	None	None	None	None	N
M/T	0.1182	likely_benign	0.1206	benign	-0.83	Destabilizing	0.086	N	0.232	neutral	N	0.342291975	None	None	N
M/V	0.1091	likely_benign	0.1032	benign	-0.905	Destabilizing	0.159	N	0.177	neutral	N	0.393510229	None	None	N
M/W	0.5156	ambiguous	0.5516	ambiguous	-0.409	Destabilizing	0.968	D	0.341	neutral	None	None	None	None	N
M/Y	0.5076	ambiguous	0.5426	ambiguous	-0.411	Destabilizing	0.896	D	0.358	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.