TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28968	87127;87128;87129	chr2:178558557;178558556;178558555	chr2:179423284;179423283;179423282
N2AB	27327	82204;82205;82206	chr2:178558557;178558556;178558555	chr2:179423284;179423283;179423282
N2A	26400	79423;79424;79425	chr2:178558557;178558556;178558555	chr2:179423284;179423283;179423282
N2B	19903	59932;59933;59934	chr2:178558557;178558556;178558555	chr2:179423284;179423283;179423282
Novex-1	20028	60307;60308;60309	chr2:178558557;178558556;178558555	chr2:179423284;179423283;179423282
Novex-2	20095	60508;60509;60510	chr2:178558557;178558556;178558555	chr2:179423284;179423283;179423282
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-99
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5946
• 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/P	rs754679595	None	0.998	N	0.583	0.465	0.372993862945	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/P	rs754679595	None	0.998	N	0.583	0.465	0.372993862945	gnomAD-4.0.0	1.23938E-06	None	None	None	None	I	None	2.66873E-05	0	None	0	0	None	0	0	0	0	0
H/R	rs754679595	0.075	0.967	N	0.451	0.287	0.340273420219	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
H/R	rs754679595	0.075	0.967	N	0.451	0.287	0.340273420219	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/R	rs754679595	0.075	0.967	N	0.451	0.287	0.340273420219	gnomAD-4.0.0	8.67563E-06	None	None	None	None	I	None	1.33437E-05	0	None	0	0	None	0	0	1.10187E-05	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	0.6378	likely_pathogenic	0.6381	pathogenic	0.214	Stabilizing	0.99	D	0.537	neutral	None	None	None	None	I
H/C	0.3938	ambiguous	0.3574	ambiguous	0.542	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	I
H/D	0.4674	ambiguous	0.5067	ambiguous	0.149	Stabilizing	0.957	D	0.519	neutral	N	0.423968343	None	None	I
H/E	0.6137	likely_pathogenic	0.6517	pathogenic	0.144	Stabilizing	0.894	D	0.478	neutral	None	None	None	None	I
H/F	0.3441	ambiguous	0.3463	ambiguous	0.54	Stabilizing	0.999	D	0.481	neutral	None	None	None	None	I
H/G	0.6174	likely_pathogenic	0.5953	pathogenic	-0.015	Destabilizing	0.995	D	0.543	neutral	None	None	None	None	I
H/I	0.5532	ambiguous	0.6365	pathogenic	0.772	Stabilizing	0.999	D	0.619	neutral	None	None	None	None	I
H/K	0.5343	ambiguous	0.5473	ambiguous	0.202	Stabilizing	0.951	D	0.503	neutral	None	None	None	None	I
H/L	0.3047	likely_benign	0.3687	ambiguous	0.772	Stabilizing	0.984	D	0.534	neutral	N	0.504218638	None	None	I
H/M	0.6417	likely_pathogenic	0.6753	pathogenic	0.663	Stabilizing	1.0	D	0.585	neutral	None	None	None	None	I
H/N	0.1791	likely_benign	0.1988	benign	0.3	Stabilizing	0.978	D	0.468	neutral	N	0.452501739	None	None	I
H/P	0.8421	likely_pathogenic	0.8694	pathogenic	0.611	Stabilizing	0.998	D	0.583	neutral	N	0.502295841	None	None	I
H/Q	0.4141	ambiguous	0.4074	ambiguous	0.315	Stabilizing	0.545	D	0.143	neutral	N	0.465604322	None	None	I
H/R	0.2782	likely_benign	0.2807	benign	-0.135	Destabilizing	0.967	D	0.451	neutral	N	0.478168188	None	None	I
H/S	0.4618	ambiguous	0.439	ambiguous	0.27	Stabilizing	0.99	D	0.496	neutral	None	None	None	None	I
H/T	0.5029	ambiguous	0.5355	ambiguous	0.357	Stabilizing	0.995	D	0.481	neutral	None	None	None	None	I
H/V	0.5036	ambiguous	0.5594	ambiguous	0.611	Stabilizing	0.997	D	0.55	neutral	None	None	None	None	I
H/W	0.5018	ambiguous	0.4983	ambiguous	0.478	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	I
H/Y	0.1327	likely_benign	0.1289	benign	0.85	Stabilizing	0.996	D	0.438	neutral	N	0.433801335	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.