TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23802	71629;71630;71631	chr2:178574728;178574727;178574726	chr2:179439455;179439454;179439453
N2AB	22161	66706;66707;66708	chr2:178574728;178574727;178574726	chr2:179439455;179439454;179439453
N2A	21234	63925;63926;63927	chr2:178574728;178574727;178574726	chr2:179439455;179439454;179439453
N2B	14737	44434;44435;44436	chr2:178574728;178574727;178574726	chr2:179439455;179439454;179439453
Novex-1	14862	44809;44810;44811	chr2:178574728;178574727;178574726	chr2:179439455;179439454;179439453
Novex-2	14929	45010;45011;45012	chr2:178574728;178574727;178574726	chr2:179439455;179439454;179439453
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: Fn3-60
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1068
• 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/N	rs1709454274	None	0.83	D	0.751	0.204	0.173771789658	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/N	rs1709454274	None	0.83	D	0.751	0.204	0.173771789658	gnomAD-4.0.0	6.5773E-06	None	None	None	None	N	None	2.41394E-05	0	None	0	0	None	0	0	0	0	0
K/Q	rs1168152439	None	0.83	N	0.754	0.215	0.152612264143	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/Q	rs1168152439	None	0.83	N	0.754	0.215	0.152612264143	gnomAD-4.0.0	2.56416E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78925E-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	0.6457	likely_pathogenic	0.6004	pathogenic	-1.097	Destabilizing	0.648	D	0.621	neutral	None	None	None	None	N
K/C	0.6303	likely_pathogenic	0.5878	pathogenic	-1.54	Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	N
K/D	0.9411	likely_pathogenic	0.9219	pathogenic	-1.647	Destabilizing	0.866	D	0.745	deleterious	None	None	None	None	N
K/E	0.5598	ambiguous	0.5142	ambiguous	-1.439	Destabilizing	0.41	N	0.607	neutral	N	0.504685572	None	None	N
K/F	0.8923	likely_pathogenic	0.8676	pathogenic	-0.432	Destabilizing	0.98	D	0.805	deleterious	None	None	None	None	N
K/G	0.7792	likely_pathogenic	0.7448	pathogenic	-1.515	Destabilizing	0.866	D	0.7	prob.neutral	None	None	None	None	N
K/H	0.4215	ambiguous	0.3939	ambiguous	-1.811	Destabilizing	0.98	D	0.775	deleterious	None	None	None	None	N
K/I	0.667	likely_pathogenic	0.6189	pathogenic	0.045	Stabilizing	0.908	D	0.816	deleterious	N	0.462916307	None	None	N
K/L	0.5972	likely_pathogenic	0.5826	pathogenic	0.045	Stabilizing	0.866	D	0.7	prob.neutral	None	None	None	None	N
K/M	0.3537	ambiguous	0.3505	ambiguous	-0.344	Destabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
K/N	0.8021	likely_pathogenic	0.765	pathogenic	-1.735	Destabilizing	0.83	D	0.751	deleterious	D	0.524138125	None	None	N
K/P	0.9959	likely_pathogenic	0.9942	pathogenic	-0.311	Destabilizing	0.929	D	0.763	deleterious	None	None	None	None	N
K/Q	0.1913	likely_benign	0.1779	benign	-1.558	Destabilizing	0.83	D	0.754	deleterious	N	0.467415263	None	None	N
K/R	0.0693	likely_benign	0.0673	benign	-1.46	Destabilizing	0.01	N	0.397	neutral	N	0.369139355	None	None	N
K/S	0.6578	likely_pathogenic	0.6173	pathogenic	-2.19	Highly Destabilizing	0.648	D	0.631	neutral	None	None	None	None	N
K/T	0.3806	ambiguous	0.3614	ambiguous	-1.77	Destabilizing	0.83	D	0.713	prob.delet.	N	0.455488903	None	None	N
K/V	0.6065	likely_pathogenic	0.5732	pathogenic	-0.311	Destabilizing	0.866	D	0.737	prob.delet.	None	None	None	None	N
K/W	0.8542	likely_pathogenic	0.809	pathogenic	-0.515	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
K/Y	0.7863	likely_pathogenic	0.7531	pathogenic	-0.161	Destabilizing	0.929	D	0.793	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.