TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21166	63721;63722;63723	chr2:178587911;178587910;178587909	chr2:179452638;179452637;179452636
N2AB	19525	58798;58799;58800	chr2:178587911;178587910;178587909	chr2:179452638;179452637;179452636
N2A	18598	56017;56018;56019	chr2:178587911;178587910;178587909	chr2:179452638;179452637;179452636
N2B	12101	36526;36527;36528	chr2:178587911;178587910;178587909	chr2:179452638;179452637;179452636
Novex-1	12226	36901;36902;36903	chr2:178587911;178587910;178587909	chr2:179452638;179452637;179452636
Novex-2	12293	37102;37103;37104	chr2:178587911;178587910;178587909	chr2:179452638;179452637;179452636
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-41
• Domain position: 103
• Structural Position: 131
• Q(SASA): 0.4834
• 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/T	rs1315515272	-0.388	0.999	N	0.701	0.259	0.246773566709	gnomAD-2.1.1	4.42E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.6E-05	None	0	0	0
K/T	rs1315515272	-0.388	0.999	N	0.701	0.259	0.246773566709	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
K/T	rs1315515272	-0.388	0.999	N	0.701	0.259	0.246773566709	gnomAD-4.0.0	6.57834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.06954E-04	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	0.3198	likely_benign	0.3174	benign	-0.332	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
K/C	0.6213	likely_pathogenic	0.6291	pathogenic	-0.328	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/D	0.6918	likely_pathogenic	0.691	pathogenic	-0.096	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
K/E	0.1508	likely_benign	0.1427	benign	None	Stabilizing	0.997	D	0.688	prob.delet.	N	0.497628235	None	None	N
K/F	0.8223	likely_pathogenic	0.8126	pathogenic	0.003	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/G	0.496	ambiguous	0.4948	ambiguous	-0.69	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
K/H	0.3673	ambiguous	0.3771	ambiguous	-1.077	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
K/I	0.3288	likely_benign	0.3196	benign	0.585	Stabilizing	0.999	D	0.779	deleterious	N	0.462258572	None	None	N
K/L	0.3655	ambiguous	0.3684	ambiguous	0.585	Stabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
K/M	0.2281	likely_benign	0.2246	benign	0.382	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/N	0.5247	ambiguous	0.5347	ambiguous	-0.302	Destabilizing	0.999	D	0.733	deleterious	N	0.48649212	None	None	N
K/P	0.9337	likely_pathogenic	0.9328	pathogenic	0.31	Stabilizing	0.999	D	0.692	prob.delet.	None	None	None	None	N
K/Q	0.1138	likely_benign	0.1154	benign	-0.35	Destabilizing	0.999	D	0.765	deleterious	N	0.506999867	None	None	N
K/R	0.0821	likely_benign	0.0805	benign	-0.607	Destabilizing	0.997	D	0.646	neutral	N	0.449703789	None	None	N
K/S	0.4361	ambiguous	0.4434	ambiguous	-0.854	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
K/T	0.1532	likely_benign	0.1519	benign	-0.562	Destabilizing	0.999	D	0.701	prob.delet.	N	0.453548839	None	None	N
K/V	0.2331	likely_benign	0.2291	benign	0.31	Stabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
K/W	0.8211	likely_pathogenic	0.807	pathogenic	0.069	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/Y	0.7451	likely_pathogenic	0.7393	pathogenic	0.345	Stabilizing	1.0	D	0.763	deleterious	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.