TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6307	19144;19145;19146	chr2:178729119;178729118;178729117	chr2:179593846;179593845;179593844
N2AB	5990	18193;18194;18195	chr2:178729119;178729118;178729117	chr2:179593846;179593845;179593844
N2A	5063	15412;15413;15414	chr2:178729119;178729118;178729117	chr2:179593846;179593845;179593844
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-47
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2355
• 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/T	rs758691112	-0.426	0.012	N	0.209	0.092	0.0482279557977	gnomAD-2.1.1	2.22E-05	None	None	None	None	N	None	0	0	None	0	3.14268E-04	None	0	None	0	0	0
S/T	rs758691112	-0.426	0.012	N	0.209	0.092	0.0482279557977	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93125E-04	None	0	0	0	0	0
S/T	rs758691112	-0.426	0.012	N	0.209	0.092	0.0482279557977	gnomAD-4.0.0	2.58073E-06	None	None	None	None	N	None	0	0	None	0	4.8714E-05	None	0	0	0	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
S/A	0.0966	likely_benign	0.0941	benign	-0.692	Destabilizing	0.325	N	0.295	neutral	None	None	None	None	N
S/C	0.1506	likely_benign	0.1348	benign	-0.393	Destabilizing	0.997	D	0.346	neutral	N	0.473279844	None	None	N
S/D	0.2263	likely_benign	0.1934	benign	0.245	Stabilizing	0.842	D	0.35	neutral	None	None	None	None	N
S/E	0.3523	ambiguous	0.3099	benign	0.164	Stabilizing	0.842	D	0.35	neutral	None	None	None	None	N
S/F	0.2229	likely_benign	0.2199	benign	-1.276	Destabilizing	0.974	D	0.429	neutral	None	None	None	None	N
S/G	0.0742	likely_benign	0.0665	benign	-0.804	Destabilizing	0.002	N	0.111	neutral	N	0.452168091	None	None	N
S/H	0.2604	likely_benign	0.2348	benign	-1.372	Destabilizing	0.991	D	0.341	neutral	None	None	None	None	N
S/I	0.2071	likely_benign	0.189	benign	-0.515	Destabilizing	0.934	D	0.443	neutral	N	0.473279844	None	None	N
S/K	0.4261	ambiguous	0.3773	ambiguous	-0.405	Destabilizing	0.029	N	0.126	neutral	None	None	None	None	N
S/L	0.1431	likely_benign	0.1407	benign	-0.515	Destabilizing	0.728	D	0.455	neutral	None	None	None	None	N
S/M	0.2043	likely_benign	0.1923	benign	-0.097	Destabilizing	0.991	D	0.341	neutral	None	None	None	None	N
S/N	0.0907	likely_benign	0.0807	benign	-0.151	Destabilizing	0.801	D	0.387	neutral	N	0.494438788	None	None	N
S/P	0.6453	likely_pathogenic	0.6474	pathogenic	-0.548	Destabilizing	0.974	D	0.383	neutral	None	None	None	None	N
S/Q	0.3668	ambiguous	0.323	benign	-0.457	Destabilizing	0.949	D	0.352	neutral	None	None	None	None	N
S/R	0.3726	ambiguous	0.3351	benign	-0.255	Destabilizing	0.669	D	0.431	neutral	N	0.508426806	None	None	N
S/T	0.0802	likely_benign	0.0775	benign	-0.329	Destabilizing	0.012	N	0.209	neutral	N	0.496671017	None	None	N
S/V	0.2121	likely_benign	0.1965	benign	-0.548	Destabilizing	0.728	D	0.442	neutral	None	None	None	None	N
S/W	0.3957	ambiguous	0.3914	ambiguous	-1.189	Destabilizing	0.998	D	0.489	neutral	None	None	None	None	N
S/Y	0.1693	likely_benign	0.1665	benign	-0.935	Destabilizing	0.991	D	0.428	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.