TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17200	51823;51824;51825	chr2:178609825;178609824;178609823	chr2:179474552;179474551;179474550
N2AB	15559	46900;46901;46902	chr2:178609825;178609824;178609823	chr2:179474552;179474551;179474550
N2A	14632	44119;44120;44121	chr2:178609825;178609824;178609823	chr2:179474552;179474551;179474550
N2B	8135	24628;24629;24630	chr2:178609825;178609824;178609823	chr2:179474552;179474551;179474550
Novex-1	8260	25003;25004;25005	chr2:178609825;178609824;178609823	chr2:179474552;179474551;179474550
Novex-2	8327	25204;25205;25206	chr2:178609825;178609824;178609823	chr2:179474552;179474551;179474550
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: Fn3-13
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.7456
• 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/Y	rs2055879782	None	None	N	0.082	0.168	0.207176502487	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
H/Y	rs2055879782	None	None	N	0.082	0.168	0.207176502487	gnomAD-4.0.0	2.03065E-06	None	None	None	None	I	None	1.74941E-05	0	None	0	0	None	0	5.16529E-04	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	0.2816	likely_benign	0.3048	benign	0.408	Stabilizing	0.025	N	0.181	neutral	None	None	None	None	I
H/C	0.2842	likely_benign	0.2712	benign	0.528	Stabilizing	0.859	D	0.228	neutral	None	None	None	None	I
H/D	0.2806	likely_benign	0.2871	benign	-0.18	Destabilizing	0.175	N	0.287	neutral	N	0.398208681	None	None	I
H/E	0.3465	ambiguous	0.3528	ambiguous	-0.186	Destabilizing	0.104	N	0.14	neutral	None	None	None	None	I
H/F	0.2271	likely_benign	0.2319	benign	0.816	Stabilizing	None	N	0.074	neutral	None	None	None	None	I
H/G	0.3548	ambiguous	0.3798	ambiguous	0.21	Stabilizing	0.055	N	0.171	neutral	None	None	None	None	I
H/I	0.3217	likely_benign	0.3271	benign	0.884	Stabilizing	0.055	N	0.271	neutral	None	None	None	None	I
H/K	0.3055	likely_benign	0.3102	benign	0.322	Stabilizing	0.104	N	0.27	neutral	None	None	None	None	I
H/L	0.1987	likely_benign	0.2022	benign	0.884	Stabilizing	0.019	N	0.231	neutral	N	0.428398302	None	None	I
H/M	0.3977	ambiguous	0.3996	ambiguous	0.594	Stabilizing	0.667	D	0.254	neutral	None	None	None	None	I
H/N	0.0989	likely_benign	0.1008	benign	0.221	Stabilizing	0.081	N	0.158	neutral	N	0.396709958	None	None	I
H/P	0.5747	likely_pathogenic	0.5712	pathogenic	0.748	Stabilizing	0.301	N	0.351	neutral	N	0.432222467	None	None	I
H/Q	0.1887	likely_benign	0.1855	benign	0.26	Stabilizing	0.301	N	0.237	neutral	N	0.426782149	None	None	I
H/R	0.1764	likely_benign	0.1693	benign	-0.096	Destabilizing	0.175	N	0.18	neutral	N	0.409465825	None	None	I
H/S	0.2047	likely_benign	0.2233	benign	0.328	Stabilizing	0.002	N	0.099	neutral	None	None	None	None	I
H/T	0.2209	likely_benign	0.2356	benign	0.41	Stabilizing	0.055	N	0.227	neutral	None	None	None	None	I
H/V	0.2389	likely_benign	0.2449	benign	0.748	Stabilizing	0.055	N	0.233	neutral	None	None	None	None	I
H/W	0.4455	ambiguous	0.4548	ambiguous	0.676	Stabilizing	0.667	D	0.239	neutral	None	None	None	None	I
H/Y	0.0979	likely_benign	0.0987	benign	0.965	Stabilizing	None	N	0.082	neutral	N	0.421645688	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.