TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18120	54583;54584;54585	chr2:178604731;178604730;178604729	chr2:179469458;179469457;179469456
N2AB	16479	49660;49661;49662	chr2:178604731;178604730;178604729	chr2:179469458;179469457;179469456
N2A	15552	46879;46880;46881	chr2:178604731;178604730;178604729	chr2:179469458;179469457;179469456
N2B	9055	27388;27389;27390	chr2:178604731;178604730;178604729	chr2:179469458;179469457;179469456
Novex-1	9180	27763;27764;27765	chr2:178604731;178604730;178604729	chr2:179469458;179469457;179469456
Novex-2	9247	27964;27965;27966	chr2:178604731;178604730;178604729	chr2:179469458;179469457;179469456
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-19
• Domain position: 56
• Structural Position: 75
• Q(SASA): 0.5924
• Predicted PPI site: I

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/A	None	None	0.005	N	0.157	0.101	0.1749357433	gnomAD-4.0.0	1.37054E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00476E-07	1.16433E-05	0
T/S	rs770883968	-0.184	None	N	0.101	0.104	0.136095386433	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/S	rs770883968	-0.184	None	N	0.101	0.104	0.136095386433	gnomAD-4.0.0	6.8527E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00476E-07	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	0.0759	likely_benign	0.0762	benign	-0.501	Destabilizing	0.005	N	0.157	neutral	N	0.455142186	None	None	I
T/C	0.3371	likely_benign	0.3063	benign	-0.181	Destabilizing	0.001	N	0.197	neutral	None	None	None	None	I
T/D	0.3611	ambiguous	0.3396	benign	-0.137	Destabilizing	0.038	N	0.277	neutral	None	None	None	None	I
T/E	0.3071	likely_benign	0.2986	benign	-0.2	Destabilizing	0.038	N	0.298	neutral	None	None	None	None	I
T/F	0.2351	likely_benign	0.2302	benign	-0.826	Destabilizing	0.214	N	0.348	neutral	None	None	None	None	I
T/G	0.2091	likely_benign	0.2043	benign	-0.677	Destabilizing	None	N	0.186	neutral	None	None	None	None	I
T/H	0.2469	likely_benign	0.2506	benign	-0.96	Destabilizing	0.676	D	0.301	neutral	None	None	None	None	I
T/I	0.1845	likely_benign	0.1834	benign	-0.145	Destabilizing	None	N	0.171	neutral	N	0.463801742	None	None	I
T/K	0.2213	likely_benign	0.236	benign	-0.577	Destabilizing	0.038	N	0.298	neutral	None	None	None	None	I
T/L	0.1014	likely_benign	0.1025	benign	-0.145	Destabilizing	0.016	N	0.261	neutral	None	None	None	None	I
T/M	0.0958	likely_benign	0.0918	benign	0.146	Stabilizing	0.214	N	0.324	neutral	None	None	None	None	I
T/N	0.113	likely_benign	0.1137	benign	-0.297	Destabilizing	0.029	N	0.209	neutral	N	0.415701151	None	None	I
T/P	0.43	ambiguous	0.43	ambiguous	-0.234	Destabilizing	0.171	N	0.397	neutral	N	0.461622654	None	None	I
T/Q	0.2219	likely_benign	0.2308	benign	-0.547	Destabilizing	0.214	N	0.372	neutral	None	None	None	None	I
T/R	0.2004	likely_benign	0.2153	benign	-0.237	Destabilizing	0.214	N	0.394	neutral	None	None	None	None	I
T/S	0.099	likely_benign	0.0947	benign	-0.499	Destabilizing	None	N	0.101	neutral	N	0.416698441	None	None	I
T/V	0.1318	likely_benign	0.132	benign	-0.234	Destabilizing	0.016	N	0.182	neutral	None	None	None	None	I
T/W	0.587	likely_pathogenic	0.5618	ambiguous	-0.807	Destabilizing	0.864	D	0.335	neutral	None	None	None	None	I
T/Y	0.2367	likely_benign	0.2403	benign	-0.568	Destabilizing	0.356	N	0.329	neutral	None	None	None	None	I

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.