TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14801	44626;44627;44628	chr2:178629324;178629323;178629322	chr2:179494051;179494050;179494049
N2AB	13160	39703;39704;39705	chr2:178629324;178629323;178629322	chr2:179494051;179494050;179494049
N2A	12233	36922;36923;36924	chr2:178629324;178629323;178629322	chr2:179494051;179494050;179494049
N2B	5736	17431;17432;17433	chr2:178629324;178629323;178629322	chr2:179494051;179494050;179494049
Novex-1	5861	17806;17807;17808	chr2:178629324;178629323;178629322	chr2:179494051;179494050;179494049
Novex-2	5928	18007;18008;18009	chr2:178629324;178629323;178629322	chr2:179494051;179494050;179494049
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-99
• Domain position: 37
• Structural Position: 55
• Q(SASA): 0.6711
• Predicted PPI site: N

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
K/E	rs1313794493	0.408	0.101	N	0.362	0.16	0.243398259712	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14916E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs1313794493	0.408	0.101	N	0.362	0.16	0.243398259712	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs1313794493	0.408	0.101	N	0.362	0.16	0.243398259712	gnomAD-4.0.0	6.57652E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	0	0	0
K/R	None	None	0.007	N	0.257	0.084	0.292787519742	gnomAD-4.0.0	3.18748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72502E-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
K/A	0.2383	likely_benign	0.2703	benign	-0.261	Destabilizing	0.129	N	0.317	neutral	None	None	None	None	N
K/C	0.5832	likely_pathogenic	0.5784	pathogenic	-0.587	Destabilizing	0.983	D	0.293	neutral	None	None	None	None	N
K/D	0.3772	ambiguous	0.3985	ambiguous	0.199	Stabilizing	0.418	N	0.349	neutral	None	None	None	None	N
K/E	0.096	likely_benign	0.0976	benign	0.283	Stabilizing	0.101	N	0.362	neutral	N	0.469217228	None	None	N
K/F	0.634	likely_pathogenic	0.65	pathogenic	-0.213	Destabilizing	0.836	D	0.316	neutral	None	None	None	None	N
K/G	0.3467	ambiguous	0.3777	ambiguous	-0.532	Destabilizing	0.264	N	0.363	neutral	None	None	None	None	N
K/H	0.2393	likely_benign	0.2323	benign	-0.601	Destabilizing	0.836	D	0.31	neutral	None	None	None	None	N
K/I	0.2138	likely_benign	0.2124	benign	0.404	Stabilizing	0.716	D	0.336	neutral	None	None	None	None	N
K/L	0.2332	likely_benign	0.2541	benign	0.404	Stabilizing	0.418	N	0.362	neutral	None	None	None	None	N
K/M	0.1498	likely_benign	0.1578	benign	-0.064	Destabilizing	0.794	D	0.309	neutral	N	0.517044489	None	None	N
K/N	0.1959	likely_benign	0.2164	benign	-0.257	Destabilizing	0.213	N	0.272	neutral	N	0.511970565	None	None	N
K/P	0.8334	likely_pathogenic	0.8677	pathogenic	0.211	Stabilizing	0.593	D	0.361	neutral	None	None	None	None	N
K/Q	0.08	likely_benign	0.0808	benign	-0.26	Destabilizing	0.007	N	0.17	neutral	N	0.44537127	None	None	N
K/R	0.0837	likely_benign	0.0776	benign	-0.157	Destabilizing	0.007	N	0.257	neutral	N	0.507225092	None	None	N
K/S	0.2485	likely_benign	0.2711	benign	-0.805	Destabilizing	0.01	N	0.214	neutral	None	None	None	None	N
K/T	0.1094	likely_benign	0.1218	benign	-0.537	Destabilizing	0.003	N	0.179	neutral	N	0.485925319	None	None	N
K/V	0.1888	likely_benign	0.1908	benign	0.211	Stabilizing	0.418	N	0.364	neutral	None	None	None	None	N
K/W	0.6864	likely_pathogenic	0.6847	pathogenic	-0.214	Destabilizing	0.983	D	0.307	neutral	None	None	None	None	N
K/Y	0.5264	ambiguous	0.5234	ambiguous	0.115	Stabilizing	0.94	D	0.309	neutral	None	None	None	None	N

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.