TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33720	101383;101384;101385	chr2:178535457;178535456;178535455	chr2:179400184;179400183;179400182
N2AB	32079	96460;96461;96462	chr2:178535457;178535456;178535455	chr2:179400184;179400183;179400182
N2A	31152	93679;93680;93681	chr2:178535457;178535456;178535455	chr2:179400184;179400183;179400182
N2B	24655	74188;74189;74190	chr2:178535457;178535456;178535455	chr2:179400184;179400183;179400182
Novex-1	24780	74563;74564;74565	chr2:178535457;178535456;178535455	chr2:179400184;179400183;179400182
Novex-2	24847	74764;74765;74766	chr2:178535457;178535456;178535455	chr2:179400184;179400183;179400182
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: Fn3-132
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.699
• 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/R	rs727503535	0.229	None	N	0.12	0.127	0.295623431141	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	1.45028E-04	None	0	0	None	0	None	0	0	0
K/R	rs727503535	0.229	None	N	0.12	0.127	0.295623431141	gnomAD-4.0.0	9.54678E-06	None	None	None	None	N	None	0	1.37206E-04	None	0	0	None	0	0	0	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	0.2893	likely_benign	0.2786	benign	0.023	Stabilizing	0.528	D	0.447	neutral	None	None	None	None	N
K/C	0.7251	likely_pathogenic	0.6655	pathogenic	-0.109	Destabilizing	0.996	D	0.469	neutral	None	None	None	None	N
K/D	0.4931	ambiguous	0.5113	ambiguous	0.17	Stabilizing	0.008	N	0.217	neutral	None	None	None	None	N
K/E	0.1668	likely_benign	0.1709	benign	0.182	Stabilizing	0.113	N	0.387	neutral	N	0.376910689	None	None	N
K/F	0.8037	likely_pathogenic	0.7632	pathogenic	-0.181	Destabilizing	0.959	D	0.471	neutral	None	None	None	None	N
K/G	0.4499	ambiguous	0.4114	ambiguous	-0.186	Destabilizing	0.528	D	0.481	neutral	None	None	None	None	N
K/H	0.3479	ambiguous	0.3143	benign	-0.504	Destabilizing	0.889	D	0.446	neutral	None	None	None	None	N
K/I	0.3622	ambiguous	0.351	ambiguous	0.497	Stabilizing	0.3	N	0.499	neutral	N	0.485081091	None	None	N
K/L	0.3907	ambiguous	0.365	ambiguous	0.497	Stabilizing	0.074	N	0.528	neutral	None	None	None	None	N
K/M	0.3004	likely_benign	0.2785	benign	0.321	Stabilizing	0.964	D	0.438	neutral	None	None	None	None	N
K/N	0.371	ambiguous	0.3825	ambiguous	0.325	Stabilizing	0.011	N	0.107	neutral	N	0.43446027	None	None	N
K/P	0.3971	ambiguous	0.409	ambiguous	0.368	Stabilizing	0.983	D	0.448	neutral	None	None	None	None	N
K/Q	0.1407	likely_benign	0.1296	benign	0.154	Stabilizing	0.198	N	0.407	neutral	N	0.451083161	None	None	N
K/R	0.0818	likely_benign	0.0734	benign	0.022	Stabilizing	None	N	0.12	neutral	N	0.427534297	None	None	N
K/S	0.3656	ambiguous	0.3512	ambiguous	-0.185	Destabilizing	0.528	D	0.369	neutral	None	None	None	None	N
K/T	0.1805	likely_benign	0.188	benign	-0.018	Destabilizing	0.38	N	0.483	neutral	N	0.446600061	None	None	N
K/V	0.3023	likely_benign	0.2997	benign	0.368	Stabilizing	0.427	N	0.473	neutral	None	None	None	None	N
K/W	0.8218	likely_pathogenic	0.764	pathogenic	-0.191	Destabilizing	0.997	D	0.549	neutral	None	None	None	None	N
K/Y	0.6933	likely_pathogenic	0.6404	pathogenic	0.172	Stabilizing	0.732	D	0.483	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.