TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24466	73621;73622;73623	chr2:178572736;178572735;178572734	chr2:179437463;179437462;179437461
N2AB	22825	68698;68699;68700	chr2:178572736;178572735;178572734	chr2:179437463;179437462;179437461
N2A	21898	65917;65918;65919	chr2:178572736;178572735;178572734	chr2:179437463;179437462;179437461
N2B	15401	46426;46427;46428	chr2:178572736;178572735;178572734	chr2:179437463;179437462;179437461
Novex-1	15526	46801;46802;46803	chr2:178572736;178572735;178572734	chr2:179437463;179437462;179437461
Novex-2	15593	47002;47003;47004	chr2:178572736;178572735;178572734	chr2:179437463;179437462;179437461
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-132
• Domain position: 36
• Structural Position: 52
• Q(SASA): 0.9036
• 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
H/N	rs756789484	0.221	0.002	N	0.205	0.097	0.101711395817	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
H/Q	rs375373437	0.289	0.642	N	0.297	0.174	0.0666544352282	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
H/R	None	None	0.473	N	0.227	0.28	0.158396225186	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	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
H/A	0.1154	likely_benign	0.1379	benign	0.333	Stabilizing	0.495	N	0.317	neutral	None	None	None	None	N
H/C	0.1082	likely_benign	0.1275	benign	0.482	Stabilizing	0.995	D	0.324	neutral	None	None	None	None	N
H/D	0.0849	likely_benign	0.0985	benign	-0.188	Destabilizing	0.002	N	0.197	neutral	N	0.267595776	None	None	N
H/E	0.1384	likely_benign	0.1643	benign	-0.198	Destabilizing	0.329	N	0.3	neutral	None	None	None	None	N
H/F	0.221	likely_benign	0.264	benign	0.711	Stabilizing	0.981	D	0.317	neutral	None	None	None	None	N
H/G	0.1115	likely_benign	0.1236	benign	0.137	Stabilizing	0.329	N	0.333	neutral	None	None	None	None	N
H/I	0.1966	likely_benign	0.2434	benign	0.801	Stabilizing	0.981	D	0.334	neutral	None	None	None	None	N
H/K	0.1295	likely_benign	0.1453	benign	0.259	Stabilizing	0.013	N	0.202	neutral	None	None	None	None	N
H/L	0.1002	likely_benign	0.1144	benign	0.801	Stabilizing	0.784	D	0.334	neutral	N	0.427405719	None	None	N
H/M	0.2723	likely_benign	0.3124	benign	0.557	Stabilizing	0.981	D	0.297	neutral	None	None	None	None	N
H/N	0.0498	likely_benign	0.052	benign	0.198	Stabilizing	0.002	N	0.205	neutral	N	0.337610434	None	None	N
H/P	0.144	likely_benign	0.1649	benign	0.667	Stabilizing	0.917	D	0.358	neutral	N	0.445914122	None	None	N
H/Q	0.0925	likely_benign	0.1037	benign	0.217	Stabilizing	0.642	D	0.297	neutral	N	0.41611129	None	None	N
H/R	0.0772	likely_benign	0.0842	benign	-0.103	Destabilizing	0.473	N	0.227	neutral	N	0.445567406	None	None	N
H/S	0.0896	likely_benign	0.0994	benign	0.279	Stabilizing	0.329	N	0.323	neutral	None	None	None	None	N
H/T	0.1059	likely_benign	0.1245	benign	0.355	Stabilizing	0.704	D	0.343	neutral	None	None	None	None	N
H/V	0.1548	likely_benign	0.1872	benign	0.667	Stabilizing	0.828	D	0.356	neutral	None	None	None	None	N
H/W	0.3617	ambiguous	0.4177	ambiguous	0.586	Stabilizing	0.995	D	0.329	neutral	None	None	None	None	N
H/Y	0.099	likely_benign	0.1139	benign	0.881	Stabilizing	0.917	D	0.319	neutral	N	0.446260839	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.