TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35676	107251;107252;107253	chr2:178528725;178528724;178528723	chr2:179393452;179393451;179393450
N2AB	34035	102328;102329;102330	chr2:178528725;178528724;178528723	chr2:179393452;179393451;179393450
N2A	33108	99547;99548;99549	chr2:178528725;178528724;178528723	chr2:179393452;179393451;179393450
N2B	26611	80056;80057;80058	chr2:178528725;178528724;178528723	chr2:179393452;179393451;179393450
Novex-1	26736	80431;80432;80433	chr2:178528725;178528724;178528723	chr2:179393452;179393451;179393450
Novex-2	26803	80632;80633;80634	chr2:178528725;178528724;178528723	chr2:179393452;179393451;179393450
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-167
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.123
• 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
T/I	rs764714213	0.399	0.497	N	0.722	0.199	0.320256813643	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.16394E-04	None	0	0	None	0	None	0	0	0
T/I	rs764714213	0.399	0.497	N	0.722	0.199	0.320256813643	gnomAD-4.0.0	6.36772E-06	None	None	None	None	N	None	0	9.15499E-05	None	0	0	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
T/A	0.1627	likely_benign	0.1879	benign	-1.121	Destabilizing	0.055	N	0.662	neutral	N	0.465332176	None	None	N
T/C	0.7328	likely_pathogenic	0.7771	pathogenic	-0.673	Destabilizing	0.909	D	0.705	prob.neutral	None	None	None	None	N
T/D	0.7504	likely_pathogenic	0.8144	pathogenic	-1.607	Destabilizing	0.157	N	0.707	prob.neutral	None	None	None	None	N
T/E	0.5713	likely_pathogenic	0.6501	pathogenic	-1.368	Destabilizing	0.157	N	0.702	prob.neutral	None	None	None	None	N
T/F	0.4601	ambiguous	0.5282	ambiguous	-0.736	Destabilizing	0.726	D	0.763	deleterious	None	None	None	None	N
T/G	0.5514	ambiguous	0.6114	pathogenic	-1.551	Destabilizing	0.157	N	0.713	prob.delet.	None	None	None	None	N
T/H	0.4449	ambiguous	0.5286	ambiguous	-1.636	Destabilizing	0.909	D	0.739	prob.delet.	None	None	None	None	N
T/I	0.3409	ambiguous	0.3642	ambiguous	0.023	Stabilizing	0.497	N	0.722	prob.delet.	N	0.46498546	None	None	N
T/K	0.5163	ambiguous	0.5961	pathogenic	-0.298	Destabilizing	0.157	N	0.703	prob.neutral	None	None	None	None	N
T/L	0.237	likely_benign	0.2523	benign	0.023	Stabilizing	0.272	N	0.709	prob.delet.	None	None	None	None	N
T/M	0.1808	likely_benign	0.1933	benign	-0.146	Destabilizing	0.968	D	0.707	prob.neutral	None	None	None	None	N
T/N	0.288	likely_benign	0.3578	ambiguous	-1.103	Destabilizing	0.331	N	0.689	prob.neutral	N	0.46602561	None	None	N
T/P	0.8169	likely_pathogenic	0.8565	pathogenic	-0.329	Destabilizing	0.001	N	0.431	neutral	N	0.466198968	None	None	N
T/Q	0.4214	ambiguous	0.4864	ambiguous	-0.774	Destabilizing	0.567	D	0.728	prob.delet.	None	None	None	None	N
T/R	0.4085	ambiguous	0.4892	ambiguous	-0.664	Destabilizing	0.567	D	0.73	prob.delet.	None	None	None	None	N
T/S	0.1784	likely_benign	0.2109	benign	-1.287	Destabilizing	0.001	N	0.466	neutral	N	0.464292026	None	None	N
T/V	0.2939	likely_benign	0.3047	benign	-0.329	Destabilizing	0.272	N	0.653	neutral	None	None	None	None	N
T/W	0.787	likely_pathogenic	0.8276	pathogenic	-0.984	Destabilizing	0.968	D	0.742	deleterious	None	None	None	None	N
T/Y	0.4679	ambiguous	0.5313	ambiguous	-0.547	Destabilizing	0.726	D	0.761	deleterious	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.