TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21348	64267;64268;64269	chr2:178587169;178587168;178587167	chr2:179451896;179451895;179451894
N2AB	19707	59344;59345;59346	chr2:178587169;178587168;178587167	chr2:179451896;179451895;179451894
N2A	18780	56563;56564;56565	chr2:178587169;178587168;178587167	chr2:179451896;179451895;179451894
N2B	12283	37072;37073;37074	chr2:178587169;178587168;178587167	chr2:179451896;179451895;179451894
Novex-1	12408	37447;37448;37449	chr2:178587169;178587168;178587167	chr2:179451896;179451895;179451894
Novex-2	12475	37648;37649;37650	chr2:178587169;178587168;178587167	chr2:179451896;179451895;179451894
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-42
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.5997
• 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
P/S	rs1453250932	None	0.003	N	0.3	0.075	0.185906805712	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1453250932	None	0.003	N	0.3	0.075	0.185906805712	gnomAD-4.0.0	1.23987E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69573E-06	0	0
P/T	None	None	0.101	N	0.466	0.065	0.218112801441	gnomAD-4.0.0	1.36879E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31906E-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
P/A	0.0697	likely_benign	0.0721	benign	-1.166	Destabilizing	0.047	N	0.353	neutral	N	0.468474056	None	None	N
P/C	0.3409	ambiguous	0.3454	ambiguous	-0.824	Destabilizing	0.94	D	0.555	neutral	None	None	None	None	N
P/D	0.6288	likely_pathogenic	0.6092	pathogenic	-1.149	Destabilizing	0.418	N	0.455	neutral	None	None	None	None	N
P/E	0.371	ambiguous	0.359	ambiguous	-1.242	Destabilizing	0.418	N	0.425	neutral	None	None	None	None	N
P/F	0.4024	ambiguous	0.4276	ambiguous	-1.26	Destabilizing	0.836	D	0.561	neutral	None	None	None	None	N
P/G	0.312	likely_benign	0.3043	benign	-1.369	Destabilizing	0.129	N	0.513	neutral	None	None	None	None	N
P/H	0.2482	likely_benign	0.255	benign	-0.868	Destabilizing	0.794	D	0.548	neutral	N	0.467481217	None	None	N
P/I	0.1879	likely_benign	0.2023	benign	-0.751	Destabilizing	0.004	N	0.416	neutral	None	None	None	None	N
P/K	0.3753	ambiguous	0.3721	ambiguous	-0.906	Destabilizing	0.264	N	0.423	neutral	None	None	None	None	N
P/L	0.1054	likely_benign	0.1246	benign	-0.751	Destabilizing	0.047	N	0.457	neutral	N	0.460489291	None	None	N
P/M	0.2061	likely_benign	0.2258	benign	-0.474	Destabilizing	0.836	D	0.545	neutral	None	None	None	None	N
P/N	0.3551	ambiguous	0.3505	ambiguous	-0.624	Destabilizing	0.264	N	0.555	neutral	None	None	None	None	N
P/Q	0.1889	likely_benign	0.1967	benign	-0.946	Destabilizing	0.716	D	0.528	neutral	None	None	None	None	N
P/R	0.2648	likely_benign	0.2656	benign	-0.252	Destabilizing	0.655	D	0.551	neutral	N	0.466031184	None	None	N
P/S	0.1369	likely_benign	0.1389	benign	-1.024	Destabilizing	0.003	N	0.3	neutral	N	0.481845998	None	None	N
P/T	0.098	likely_benign	0.1017	benign	-1.021	Destabilizing	0.101	N	0.466	neutral	N	0.464164314	None	None	N
P/V	0.1385	likely_benign	0.1432	benign	-0.854	Destabilizing	0.001	N	0.367	neutral	None	None	None	None	N
P/W	0.65	likely_pathogenic	0.6717	pathogenic	-1.319	Destabilizing	0.983	D	0.565	neutral	None	None	None	None	N
P/Y	0.425	ambiguous	0.437	ambiguous	-1.043	Destabilizing	0.94	D	0.564	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.