TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30961	93106;93107;93108	chr2:178548745;178548744;178548743	chr2:179413472;179413471;179413470
N2AB	29320	88183;88184;88185	chr2:178548745;178548744;178548743	chr2:179413472;179413471;179413470
N2A	28393	85402;85403;85404	chr2:178548745;178548744;178548743	chr2:179413472;179413471;179413470
N2B	21896	65911;65912;65913	chr2:178548745;178548744;178548743	chr2:179413472;179413471;179413470
Novex-1	22021	66286;66287;66288	chr2:178548745;178548744;178548743	chr2:179413472;179413471;179413470
Novex-2	22088	66487;66488;66489	chr2:178548745;178548744;178548743	chr2:179413472;179413471;179413470
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: Ig-150
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1503
• 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/Q	None	None	0.967	N	0.583	0.387	0.28297238246	gnomAD-4.0.0	4.78976E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29623E-06	0	0
K/R	rs756055571	-0.48	0.025	N	0.261	0.16	0.264547087235	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/R	rs756055571	-0.48	0.025	N	0.261	0.16	0.264547087235	gnomAD-4.0.0	1.59149E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85819E-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	0.9772	likely_pathogenic	0.9798	pathogenic	-1.03	Destabilizing	0.916	D	0.502	neutral	None	None	None	None	N
K/C	0.9465	likely_pathogenic	0.9521	pathogenic	-1.033	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
K/D	0.996	likely_pathogenic	0.9958	pathogenic	-0.076	Destabilizing	0.987	D	0.698	prob.neutral	None	None	None	None	N
K/E	0.9722	likely_pathogenic	0.9693	pathogenic	0.042	Stabilizing	0.892	D	0.444	neutral	D	0.526981315	None	None	N
K/F	0.9835	likely_pathogenic	0.9858	pathogenic	-0.981	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
K/G	0.9847	likely_pathogenic	0.9852	pathogenic	-1.364	Destabilizing	0.975	D	0.658	neutral	None	None	None	None	N
K/H	0.7742	likely_pathogenic	0.7763	pathogenic	-1.795	Destabilizing	0.997	D	0.704	prob.neutral	None	None	None	None	N
K/I	0.9216	likely_pathogenic	0.9315	pathogenic	-0.161	Destabilizing	0.983	D	0.772	deleterious	N	0.503001257	None	None	N
K/L	0.8696	likely_pathogenic	0.8747	pathogenic	-0.161	Destabilizing	0.975	D	0.658	neutral	None	None	None	None	N
K/M	0.8353	likely_pathogenic	0.8471	pathogenic	-0.146	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
K/N	0.9822	likely_pathogenic	0.9818	pathogenic	-0.492	Destabilizing	0.967	D	0.596	neutral	D	0.526727825	None	None	N
K/P	0.9963	likely_pathogenic	0.9964	pathogenic	-0.424	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
K/Q	0.7455	likely_pathogenic	0.7514	pathogenic	-0.624	Destabilizing	0.967	D	0.583	neutral	N	0.499887385	None	None	N
K/R	0.1544	likely_benign	0.1635	benign	-0.569	Destabilizing	0.025	N	0.261	neutral	N	0.457305638	None	None	N
K/S	0.9849	likely_pathogenic	0.9856	pathogenic	-1.308	Destabilizing	0.916	D	0.515	neutral	None	None	None	None	N
K/T	0.9594	likely_pathogenic	0.9593	pathogenic	-0.977	Destabilizing	0.967	D	0.651	neutral	D	0.526474336	None	None	N
K/V	0.9073	likely_pathogenic	0.9145	pathogenic	-0.424	Destabilizing	0.987	D	0.719	prob.delet.	None	None	None	None	N
K/W	0.9852	likely_pathogenic	0.9868	pathogenic	-0.771	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
K/Y	0.9576	likely_pathogenic	0.9613	pathogenic	-0.441	Destabilizing	0.996	D	0.745	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.