TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26003	78232;78233;78234	chr2:178568125;178568124;178568123	chr2:179432852;179432851;179432850
N2AB	24362	73309;73310;73311	chr2:178568125;178568124;178568123	chr2:179432852;179432851;179432850
N2A	23435	70528;70529;70530	chr2:178568125;178568124;178568123	chr2:179432852;179432851;179432850
N2B	16938	51037;51038;51039	chr2:178568125;178568124;178568123	chr2:179432852;179432851;179432850
Novex-1	17063	51412;51413;51414	chr2:178568125;178568124;178568123	chr2:179432852;179432851;179432850
Novex-2	17130	51613;51614;51615	chr2:178568125;178568124;178568123	chr2:179432852;179432851;179432850
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-77
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2042
• 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
S/P	None	None	0.896	N	0.393	0.345	0.230578612272	gnomAD-4.0.0	1.59201E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.1187	likely_benign	0.1305	benign	-0.56	Destabilizing	0.201	N	0.401	neutral	N	0.473916906	None	None	N
S/C	0.1116	likely_benign	0.1191	benign	-0.52	Destabilizing	0.99	D	0.389	neutral	N	0.518634566	None	None	N
S/D	0.5752	likely_pathogenic	0.6515	pathogenic	-1.141	Destabilizing	0.447	N	0.376	neutral	None	None	None	None	N
S/E	0.7536	likely_pathogenic	0.8114	pathogenic	-1.134	Destabilizing	0.617	D	0.381	neutral	None	None	None	None	N
S/F	0.3183	likely_benign	0.3767	ambiguous	-0.815	Destabilizing	0.896	D	0.428	neutral	N	0.475184354	None	None	N
S/G	0.096	likely_benign	0.1013	benign	-0.811	Destabilizing	0.4	N	0.362	neutral	None	None	None	None	N
S/H	0.4415	ambiguous	0.498	ambiguous	-1.432	Destabilizing	0.92	D	0.396	neutral	None	None	None	None	N
S/I	0.4313	ambiguous	0.4843	ambiguous	0.001	Stabilizing	0.739	D	0.401	neutral	None	None	None	None	N
S/K	0.7774	likely_pathogenic	0.8217	pathogenic	-0.872	Destabilizing	0.617	D	0.387	neutral	None	None	None	None	N
S/L	0.1376	likely_benign	0.1534	benign	0.001	Stabilizing	0.447	N	0.398	neutral	None	None	None	None	N
S/M	0.2434	likely_benign	0.2637	benign	0.399	Stabilizing	0.977	D	0.39	neutral	None	None	None	None	N
S/N	0.1703	likely_benign	0.1894	benign	-1.009	Destabilizing	0.021	N	0.153	neutral	None	None	None	None	N
S/P	0.8849	likely_pathogenic	0.9224	pathogenic	-0.152	Destabilizing	0.896	D	0.393	neutral	N	0.507024771	None	None	N
S/Q	0.6308	likely_pathogenic	0.6769	pathogenic	-1.192	Destabilizing	0.92	D	0.397	neutral	None	None	None	None	N
S/R	0.7031	likely_pathogenic	0.7546	pathogenic	-0.737	Destabilizing	0.85	D	0.381	neutral	None	None	None	None	N
S/T	0.0727	likely_benign	0.0714	benign	-0.857	Destabilizing	0.001	N	0.059	neutral	N	0.410311187	None	None	N
S/V	0.3467	ambiguous	0.3915	ambiguous	-0.152	Destabilizing	0.447	N	0.392	neutral	None	None	None	None	N
S/W	0.5385	ambiguous	0.5946	pathogenic	-0.891	Destabilizing	0.992	D	0.513	neutral	None	None	None	None	N
S/Y	0.2909	likely_benign	0.3332	benign	-0.576	Destabilizing	0.896	D	0.421	neutral	N	0.478284999	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.