TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35134	105625;105626;105627	chr2:178531215;178531214;178531213	chr2:179395942;179395941;179395940
N2AB	33493	100702;100703;100704	chr2:178531215;178531214;178531213	chr2:179395942;179395941;179395940
N2A	32566	97921;97922;97923	chr2:178531215;178531214;178531213	chr2:179395942;179395941;179395940
N2B	26069	78430;78431;78432	chr2:178531215;178531214;178531213	chr2:179395942;179395941;179395940
Novex-1	26194	78805;78806;78807	chr2:178531215;178531214;178531213	chr2:179395942;179395941;179395940
Novex-2	26261	79006;79007;79008	chr2:178531215;178531214;178531213	chr2:179395942;179395941;179395940
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-164
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5994
• 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
K/M	rs1394892060	0.223	0.999	N	0.69	0.528	0.458013479912	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	1.24039E-04	0	None	0	0	None	0	None	0	0	0
K/M	rs1394892060	0.223	0.999	N	0.69	0.528	0.458013479912	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
K/M	rs1394892060	0.223	0.999	N	0.69	0.528	0.458013479912	gnomAD-4.0.0	3.8425E-06	None	None	None	None	I	None	5.07408E-05	0	None	0	0	None	0	0	0	0	0
K/T	None	None	0.322	D	0.387	0.334	0.331365685468	gnomAD-4.0.0	1.59088E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85752E-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	0.6894	likely_pathogenic	0.6697	pathogenic	-0.246	Destabilizing	0.953	D	0.614	neutral	None	None	None	None	I
K/C	0.9327	likely_pathogenic	0.9288	pathogenic	-0.328	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
K/D	0.9403	likely_pathogenic	0.939	pathogenic	0.126	Stabilizing	0.993	D	0.661	neutral	None	None	None	None	I
K/E	0.5256	ambiguous	0.5205	ambiguous	0.176	Stabilizing	0.939	D	0.625	neutral	N	0.509105249	None	None	I
K/F	0.9473	likely_pathogenic	0.9402	pathogenic	-0.218	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	I
K/G	0.846	likely_pathogenic	0.8352	pathogenic	-0.526	Destabilizing	0.976	D	0.629	neutral	None	None	None	None	I
K/H	0.6362	likely_pathogenic	0.621	pathogenic	-0.876	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	I
K/I	0.7373	likely_pathogenic	0.7171	pathogenic	0.437	Stabilizing	0.986	D	0.744	deleterious	None	None	None	None	I
K/L	0.6595	likely_pathogenic	0.6416	pathogenic	0.437	Stabilizing	0.953	D	0.634	neutral	None	None	None	None	I
K/M	0.5659	likely_pathogenic	0.5413	ambiguous	0.244	Stabilizing	0.999	D	0.69	prob.neutral	N	0.498547253	None	None	I
K/N	0.8396	likely_pathogenic	0.828	pathogenic	-0.006	Destabilizing	0.982	D	0.649	neutral	N	0.521997188	None	None	I
K/P	0.7758	likely_pathogenic	0.7961	pathogenic	0.24	Stabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	I
K/Q	0.3069	likely_benign	0.2849	benign	-0.143	Destabilizing	0.982	D	0.669	neutral	N	0.500120406	None	None	I
K/R	0.1176	likely_benign	0.1099	benign	-0.28	Destabilizing	0.1	N	0.345	neutral	N	0.486999181	None	None	I
K/S	0.7893	likely_pathogenic	0.7726	pathogenic	-0.586	Destabilizing	0.91	D	0.623	neutral	None	None	None	None	I
K/T	0.5038	ambiguous	0.489	ambiguous	-0.357	Destabilizing	0.322	N	0.387	neutral	D	0.524978779	None	None	I
K/V	0.6782	likely_pathogenic	0.6511	pathogenic	0.24	Stabilizing	0.986	D	0.615	neutral	None	None	None	None	I
K/W	0.9433	likely_pathogenic	0.9404	pathogenic	-0.147	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
K/Y	0.8741	likely_pathogenic	0.8607	pathogenic	0.173	Stabilizing	0.998	D	0.737	prob.delet.	None	None	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.