TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29000	87223;87224;87225	chr2:178558461;178558460;178558459	chr2:179423188;179423187;179423186
N2AB	27359	82300;82301;82302	chr2:178558461;178558460;178558459	chr2:179423188;179423187;179423186
N2A	26432	79519;79520;79521	chr2:178558461;178558460;178558459	chr2:179423188;179423187;179423186
N2B	19935	60028;60029;60030	chr2:178558461;178558460;178558459	chr2:179423188;179423187;179423186
Novex-1	20060	60403;60404;60405	chr2:178558461;178558460;178558459	chr2:179423188;179423187;179423186
Novex-2	20127	60604;60605;60606	chr2:178558461;178558460;178558459	chr2:179423188;179423187;179423186
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: Fn3-99
• Domain position: 59
• Structural Position: 91
• Q(SASA): 0.393
• 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
H/Q	rs758683372	None	0.907	N	0.475	0.303	0.176091768786	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
H/Q	rs758683372	None	0.907	N	0.475	0.303	0.176091768786	gnomAD-4.0.0	6.57358E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.07039E-04	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	0.2074	likely_benign	0.2221	benign	-0.987	Destabilizing	0.228	N	0.447	neutral	None	None	None	None	I
H/C	0.0855	likely_benign	0.0884	benign	-0.156	Destabilizing	0.983	D	0.562	neutral	None	None	None	None	I
H/D	0.4628	ambiguous	0.4899	ambiguous	-0.663	Destabilizing	0.523	D	0.528	neutral	N	0.46778341	None	None	I
H/E	0.3972	ambiguous	0.4119	ambiguous	-0.522	Destabilizing	0.593	D	0.34	neutral	None	None	None	None	I
H/F	0.1727	likely_benign	0.16	benign	0.57	Stabilizing	0.001	N	0.261	neutral	None	None	None	None	I
H/G	0.3472	ambiguous	0.3752	ambiguous	-1.403	Destabilizing	0.593	D	0.519	neutral	None	None	None	None	I
H/I	0.2069	likely_benign	0.1977	benign	0.189	Stabilizing	0.264	N	0.468	neutral	None	None	None	None	I
H/K	0.3882	ambiguous	0.3967	ambiguous	-0.615	Destabilizing	0.418	N	0.482	neutral	None	None	None	None	I
H/L	0.0974	likely_benign	0.0915	benign	0.189	Stabilizing	0.001	N	0.425	neutral	N	0.383663303	None	None	I
H/M	0.3502	ambiguous	0.3344	benign	-0.027	Destabilizing	0.716	D	0.553	neutral	None	None	None	None	I
H/N	0.166	likely_benign	0.1776	benign	-0.902	Destabilizing	0.523	D	0.414	neutral	N	0.515998644	None	None	I
H/P	0.665	likely_pathogenic	0.7091	pathogenic	-0.184	Destabilizing	0.921	D	0.569	neutral	N	0.515998644	None	None	I
H/Q	0.2117	likely_benign	0.2152	benign	-0.582	Destabilizing	0.907	D	0.475	neutral	N	0.478827122	None	None	I
H/R	0.1772	likely_benign	0.178	benign	-1.137	Destabilizing	0.523	D	0.455	neutral	N	0.515825286	None	None	I
H/S	0.2075	likely_benign	0.2237	benign	-0.98	Destabilizing	0.418	N	0.45	neutral	None	None	None	None	I
H/T	0.1975	likely_benign	0.2125	benign	-0.72	Destabilizing	0.593	D	0.507	neutral	None	None	None	None	I
H/V	0.1549	likely_benign	0.1524	benign	-0.184	Destabilizing	0.129	N	0.459	neutral	None	None	None	None	I
H/W	0.4087	ambiguous	0.4113	ambiguous	1.003	Stabilizing	0.836	D	0.543	neutral	None	None	None	None	I
H/Y	0.073	likely_benign	0.0692	benign	0.979	Stabilizing	0.001	N	0.137	neutral	N	0.344046122	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.