TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32664	98215;98216;98217	chr2:178540176;178540175;178540174	chr2:179404903;179404902;179404901
N2AB	31023	93292;93293;93294	chr2:178540176;178540175;178540174	chr2:179404903;179404902;179404901
N2A	30096	90511;90512;90513	chr2:178540176;178540175;178540174	chr2:179404903;179404902;179404901
N2B	23599	71020;71021;71022	chr2:178540176;178540175;178540174	chr2:179404903;179404902;179404901
Novex-1	23724	71395;71396;71397	chr2:178540176;178540175;178540174	chr2:179404903;179404902;179404901
Novex-2	23791	71596;71597;71598	chr2:178540176;178540175;178540174	chr2:179404903;179404902;179404901
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-126
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.7532
• 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/Q	rs794729549	None	1.0	N	0.703	0.22	0.146414634003	gnomAD-4.0.0	8.21042E-06	None	None	None	None	N	None	0	0	None	0	3.02267E-04	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
H/A	0.3859	ambiguous	0.421	ambiguous	0.294	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	N
H/C	0.2983	likely_benign	0.32	benign	0.396	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
H/D	0.3417	ambiguous	0.4129	ambiguous	-0.144	Destabilizing	1.0	D	0.682	prob.neutral	N	0.357322064	None	None	N
H/E	0.5515	ambiguous	0.624	pathogenic	-0.153	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
H/F	0.4602	ambiguous	0.5015	ambiguous	0.68	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
H/G	0.3339	likely_benign	0.3765	ambiguous	0.107	Stabilizing	0.999	D	0.605	neutral	None	None	None	None	N
H/I	0.6607	likely_pathogenic	0.7064	pathogenic	0.74	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
H/K	0.4584	ambiguous	0.529	ambiguous	0.232	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
H/L	0.2404	likely_benign	0.2862	benign	0.74	Stabilizing	1.0	D	0.665	neutral	N	0.490332195	None	None	N
H/M	0.6005	likely_pathogenic	0.6266	pathogenic	0.488	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
H/N	0.1097	likely_benign	0.1429	benign	0.139	Stabilizing	0.999	D	0.616	neutral	N	0.340333813	None	None	N
H/P	0.5403	ambiguous	0.5533	ambiguous	0.613	Stabilizing	1.0	D	0.644	neutral	N	0.456219622	None	None	N
H/Q	0.3222	likely_benign	0.3874	ambiguous	0.169	Stabilizing	1.0	D	0.703	prob.neutral	N	0.455699547	None	None	N
H/R	0.2518	likely_benign	0.3224	benign	-0.117	Destabilizing	1.0	D	0.714	prob.delet.	N	0.394189728	None	None	N
H/S	0.2576	likely_benign	0.2914	benign	0.191	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
H/T	0.4405	ambiguous	0.4951	ambiguous	0.268	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	N
H/V	0.5207	ambiguous	0.5693	pathogenic	0.613	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
H/W	0.6196	likely_pathogenic	0.6367	pathogenic	0.552	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
H/Y	0.1658	likely_benign	0.1971	benign	0.832	Stabilizing	0.999	D	0.613	neutral	N	0.490332195	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.