TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22751	68476;68477;68478	chr2:178578689;178578688;178578687	chr2:179443416;179443415;179443414
N2AB	21110	63553;63554;63555	chr2:178578689;178578688;178578687	chr2:179443416;179443415;179443414
N2A	20183	60772;60773;60774	chr2:178578689;178578688;178578687	chr2:179443416;179443415;179443414
N2B	13686	41281;41282;41283	chr2:178578689;178578688;178578687	chr2:179443416;179443415;179443414
Novex-1	13811	41656;41657;41658	chr2:178578689;178578688;178578687	chr2:179443416;179443415;179443414
Novex-2	13878	41857;41858;41859	chr2:178578689;178578688;178578687	chr2:179443416;179443415;179443414
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-53
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4081
• 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
N/S	rs761226149	-0.288	None	N	0.109	0.102	0.146414634003	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
N/S	rs761226149	-0.288	None	N	0.109	0.102	0.146414634003	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
N/S	rs761226149	-0.288	None	N	0.109	0.102	0.146414634003	gnomAD-4.0.0	9.92853E-06	None	None	None	None	I	None	1.33743E-05	1.67347E-05	None	0	0	None	0	0	1.1026E-05	0	1.60375E-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
N/A	0.1059	likely_benign	0.0878	benign	-0.556	Destabilizing	0.015	N	0.297	neutral	None	None	None	None	I
N/C	0.1379	likely_benign	0.114	benign	0.167	Stabilizing	0.816	D	0.457	neutral	None	None	None	None	I
N/D	0.1123	likely_benign	0.1006	benign	0.145	Stabilizing	None	N	0.092	neutral	N	0.454064751	None	None	I
N/E	0.172	likely_benign	0.1477	benign	0.185	Stabilizing	None	N	0.081	neutral	None	None	None	None	I
N/F	0.2882	likely_benign	0.2413	benign	-0.535	Destabilizing	0.54	D	0.563	neutral	None	None	None	None	I
N/G	0.1857	likely_benign	0.1573	benign	-0.831	Destabilizing	0.015	N	0.217	neutral	None	None	None	None	I
N/H	0.0656	likely_benign	0.0593	benign	-0.673	Destabilizing	0.47	N	0.361	neutral	N	0.453024601	None	None	I
N/I	0.0928	likely_benign	0.0812	benign	0.108	Stabilizing	0.059	N	0.479	neutral	N	0.447138778	None	None	I
N/K	0.1169	likely_benign	0.0981	benign	-0.065	Destabilizing	None	N	0.079	neutral	N	0.37756405	None	None	I
N/L	0.115	likely_benign	0.0993	benign	0.108	Stabilizing	0.033	N	0.371	neutral	None	None	None	None	I
N/M	0.1681	likely_benign	0.145	benign	0.35	Stabilizing	0.54	D	0.477	neutral	None	None	None	None	I
N/P	0.718	likely_pathogenic	0.684	pathogenic	-0.084	Destabilizing	0.251	N	0.514	neutral	None	None	None	None	I
N/Q	0.1303	likely_benign	0.1079	benign	-0.524	Destabilizing	0.006	N	0.13	neutral	None	None	None	None	I
N/R	0.1303	likely_benign	0.1173	benign	-0.106	Destabilizing	0.033	N	0.263	neutral	None	None	None	None	I
N/S	0.0647	likely_benign	0.0606	benign	-0.503	Destabilizing	None	N	0.109	neutral	N	0.417351802	None	None	I
N/T	0.0726	likely_benign	0.0629	benign	-0.284	Destabilizing	0.025	N	0.252	neutral	N	0.394264299	None	None	I
N/V	0.0844	likely_benign	0.0743	benign	-0.084	Destabilizing	0.001	N	0.322	neutral	None	None	None	None	I
N/W	0.5466	ambiguous	0.4877	ambiguous	-0.384	Destabilizing	0.931	D	0.483	neutral	None	None	None	None	I
N/Y	0.0981	likely_benign	0.0899	benign	-0.163	Destabilizing	0.73	D	0.586	neutral	N	0.471458433	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.