TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31434	94525;94526;94527	chr2:178547225;178547224;178547223	chr2:179411952;179411951;179411950
N2AB	29793	89602;89603;89604	chr2:178547225;178547224;178547223	chr2:179411952;179411951;179411950
N2A	28866	86821;86822;86823	chr2:178547225;178547224;178547223	chr2:179411952;179411951;179411950
N2B	22369	67330;67331;67332	chr2:178547225;178547224;178547223	chr2:179411952;179411951;179411950
Novex-1	22494	67705;67706;67707	chr2:178547225;178547224;178547223	chr2:179411952;179411951;179411950
Novex-2	22561	67906;67907;67908	chr2:178547225;178547224;178547223	chr2:179411952;179411951;179411950
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: Fn3-117
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5776
• 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	rs773946401	0.985	0.985	N	0.303	0.309	0.228597637076	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
H/Y	rs773946401	0.985	0.985	N	0.303	0.309	0.228597637076	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07297E-04	0
H/Y	rs773946401	0.985	0.985	N	0.303	0.309	0.228597637076	gnomAD-4.0.0	7.68675E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	8.04096E-05	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	0.4058	ambiguous	0.4255	ambiguous	-0.07	Destabilizing	0.025	N	0.117	neutral	None	None	None	None	I
H/C	0.2568	likely_benign	0.273	benign	0.472	Stabilizing	0.999	D	0.335	neutral	None	None	None	None	I
H/D	0.354	ambiguous	0.3731	ambiguous	0.025	Stabilizing	0.013	N	0.103	neutral	N	0.396493741	None	None	I
H/E	0.4786	ambiguous	0.526	ambiguous	0.068	Stabilizing	0.739	D	0.304	neutral	None	None	None	None	I
H/F	0.4082	ambiguous	0.4123	ambiguous	0.674	Stabilizing	0.997	D	0.365	neutral	None	None	None	None	I
H/G	0.4911	ambiguous	0.5006	ambiguous	-0.372	Destabilizing	0.85	D	0.383	neutral	None	None	None	None	I
H/I	0.4686	ambiguous	0.5421	ambiguous	0.714	Stabilizing	0.99	D	0.434	neutral	None	None	None	None	I
H/K	0.4771	ambiguous	0.5456	ambiguous	-0.01	Destabilizing	0.932	D	0.379	neutral	None	None	None	None	I
H/L	0.2108	likely_benign	0.239	benign	0.714	Stabilizing	0.912	D	0.441	neutral	N	0.474858524	None	None	I
H/M	0.5651	likely_pathogenic	0.6124	pathogenic	0.536	Stabilizing	0.997	D	0.345	neutral	None	None	None	None	I
H/N	0.1273	likely_benign	0.1507	benign	-0.017	Destabilizing	0.055	N	0.061	neutral	N	0.397552533	None	None	I
H/P	0.7914	likely_pathogenic	0.8099	pathogenic	0.478	Stabilizing	0.955	D	0.425	neutral	N	0.489635975	None	None	I
H/Q	0.2758	likely_benign	0.3122	benign	0.113	Stabilizing	0.982	D	0.296	neutral	N	0.45913971	None	None	I
H/R	0.2266	likely_benign	0.2598	benign	-0.523	Destabilizing	0.955	D	0.249	neutral	N	0.447461279	None	None	I
H/S	0.2512	likely_benign	0.2705	benign	-0.021	Destabilizing	0.739	D	0.362	neutral	None	None	None	None	I
H/T	0.3412	ambiguous	0.3895	ambiguous	0.127	Stabilizing	0.85	D	0.402	neutral	None	None	None	None	I
H/V	0.3878	ambiguous	0.4487	ambiguous	0.478	Stabilizing	0.932	D	0.475	neutral	None	None	None	None	I
H/W	0.5828	likely_pathogenic	0.564	pathogenic	0.761	Stabilizing	0.999	D	0.365	neutral	None	None	None	None	I
H/Y	0.1573	likely_benign	0.1602	benign	1.006	Stabilizing	0.985	D	0.303	neutral	N	0.392589431	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.