TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17515	52768;52769;52770	chr2:178608340;178608339;178608338	chr2:179473067;179473066;179473065
N2AB	15874	47845;47846;47847	chr2:178608340;178608339;178608338	chr2:179473067;179473066;179473065
N2A	14947	45064;45065;45066	chr2:178608340;178608339;178608338	chr2:179473067;179473066;179473065
N2B	8450	25573;25574;25575	chr2:178608340;178608339;178608338	chr2:179473067;179473066;179473065
Novex-1	8575	25948;25949;25950	chr2:178608340;178608339;178608338	chr2:179473067;179473066;179473065
Novex-2	8642	26149;26150;26151	chr2:178608340;178608339;178608338	chr2:179473067;179473066;179473065
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: Fn3-15
• Domain position: 46
• Structural Position: 64
• Q(SASA): 0.5779
• 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/N	rs1576373600	None	0.99	N	0.451	0.35	0.269558022972	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
H/N	rs1576373600	None	0.99	N	0.451	0.35	0.269558022972	gnomAD-4.0.0	4.34181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	7.69366E-05	0
H/P	None	None	0.999	N	0.563	0.515	0.397838977388	gnomAD-4.0.0	6.84776E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99892E-07	0	0
H/R	rs1319404770	-0.24	0.135	N	0.301	0.268	0.178374595973	gnomAD-4.0.0	4.79343E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29925E-06	0	0
H/Y	None	None	0.997	N	0.405	0.479	0.313210971179	gnomAD-4.0.0	2.05436E-06	None	None	None	None	I	None	0	0	None	0	2.53575E-05	None	0	0	1.79978E-06	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	0.7476	likely_pathogenic	0.6092	pathogenic	0.289	Stabilizing	0.993	D	0.459	neutral	None	None	None	None	I
H/C	0.4464	ambiguous	0.3644	ambiguous	0.607	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	I
H/D	0.8681	likely_pathogenic	0.7454	pathogenic	-0.035	Destabilizing	0.997	D	0.412	neutral	N	0.429723667	None	None	I
H/E	0.8829	likely_pathogenic	0.7741	pathogenic	-0.018	Destabilizing	0.985	D	0.404	neutral	None	None	None	None	I
H/F	0.4395	ambiguous	0.4215	ambiguous	0.894	Stabilizing	0.999	D	0.444	neutral	None	None	None	None	I
H/G	0.7975	likely_pathogenic	0.6908	pathogenic	0.034	Stabilizing	0.993	D	0.456	neutral	None	None	None	None	I
H/I	0.6375	likely_pathogenic	0.5371	ambiguous	0.929	Stabilizing	0.999	D	0.619	neutral	None	None	None	None	I
H/K	0.7208	likely_pathogenic	0.5721	pathogenic	0.27	Stabilizing	0.971	D	0.42	neutral	None	None	None	None	I
H/L	0.3388	likely_benign	0.272	benign	0.929	Stabilizing	0.997	D	0.535	neutral	N	0.410812619	None	None	I
H/M	0.7392	likely_pathogenic	0.6676	pathogenic	0.662	Stabilizing	1.0	D	0.579	neutral	None	None	None	None	I
H/N	0.4025	ambiguous	0.2976	benign	0.197	Stabilizing	0.99	D	0.451	neutral	N	0.442519606	None	None	I
H/P	0.8274	likely_pathogenic	0.7217	pathogenic	0.74	Stabilizing	0.999	D	0.563	neutral	N	0.451293804	None	None	I
H/Q	0.5959	likely_pathogenic	0.471	ambiguous	0.281	Stabilizing	0.994	D	0.403	neutral	N	0.439113941	None	None	I
H/R	0.3818	ambiguous	0.2687	benign	-0.231	Destabilizing	0.135	N	0.301	neutral	N	0.374910534	None	None	I
H/S	0.6671	likely_pathogenic	0.5322	ambiguous	0.273	Stabilizing	0.993	D	0.415	neutral	None	None	None	None	I
H/T	0.7378	likely_pathogenic	0.6135	pathogenic	0.391	Stabilizing	0.998	D	0.493	neutral	None	None	None	None	I
H/V	0.5823	likely_pathogenic	0.46	ambiguous	0.74	Stabilizing	0.998	D	0.625	neutral	None	None	None	None	I
H/W	0.5622	ambiguous	0.5348	ambiguous	0.856	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	I
H/Y	0.163	likely_benign	0.1488	benign	1.126	Stabilizing	0.997	D	0.405	neutral	N	0.476768252	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.