TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29152	87679;87680;87681	chr2:178557900;178557899;178557898	chr2:179422627;179422626;179422625
N2AB	27511	82756;82757;82758	chr2:178557900;178557899;178557898	chr2:179422627;179422626;179422625
N2A	26584	79975;79976;79977	chr2:178557900;178557899;178557898	chr2:179422627;179422626;179422625
N2B	20087	60484;60485;60486	chr2:178557900;178557899;178557898	chr2:179422627;179422626;179422625
Novex-1	20212	60859;60860;60861	chr2:178557900;178557899;178557898	chr2:179422627;179422626;179422625
Novex-2	20279	61060;61061;61062	chr2:178557900;178557899;178557898	chr2:179422627;179422626;179422625
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-100
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.381
• 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
E/K	rs752325107	0.163	0.928	N	0.473	0.244	0.297375071883	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.66945E-04	None	0	None	0	0	0
E/K	rs752325107	0.163	0.928	N	0.473	0.244	0.297375071883	gnomAD-4.0.0	1.59191E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	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
E/A	0.1531	likely_benign	0.1592	benign	-0.515	Destabilizing	0.039	N	0.377	neutral	N	0.38618632	None	None	N
E/C	0.8712	likely_pathogenic	0.8823	pathogenic	0.051	Stabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
E/D	0.2441	likely_benign	0.2785	benign	-0.445	Destabilizing	0.963	D	0.393	neutral	N	0.455739619	None	None	N
E/F	0.9284	likely_pathogenic	0.9361	pathogenic	-0.459	Destabilizing	0.992	D	0.792	deleterious	None	None	None	None	N
E/G	0.1923	likely_benign	0.2012	benign	-0.73	Destabilizing	0.865	D	0.615	neutral	N	0.448640288	None	None	N
E/H	0.6608	likely_pathogenic	0.6943	pathogenic	-0.441	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
E/I	0.6233	likely_pathogenic	0.6655	pathogenic	0.023	Stabilizing	0.983	D	0.772	deleterious	None	None	None	None	N
E/K	0.1907	likely_benign	0.2104	benign	0.314	Stabilizing	0.928	D	0.473	neutral	N	0.442522393	None	None	N
E/L	0.6199	likely_pathogenic	0.6554	pathogenic	0.023	Stabilizing	0.968	D	0.703	prob.neutral	None	None	None	None	N
E/M	0.6196	likely_pathogenic	0.653	pathogenic	0.293	Stabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
E/N	0.4062	ambiguous	0.4513	ambiguous	-0.002	Destabilizing	0.992	D	0.668	neutral	None	None	None	None	N
E/P	0.5403	ambiguous	0.574	pathogenic	-0.136	Destabilizing	0.992	D	0.68	prob.neutral	None	None	None	None	N
E/Q	0.1872	likely_benign	0.1959	benign	0.021	Stabilizing	0.989	D	0.623	neutral	N	0.502301415	None	None	N
E/R	0.3425	ambiguous	0.358	ambiguous	0.41	Stabilizing	0.983	D	0.669	neutral	None	None	None	None	N
E/S	0.2362	likely_benign	0.2461	benign	-0.174	Destabilizing	0.895	D	0.465	neutral	None	None	None	None	N
E/T	0.3151	likely_benign	0.348	ambiguous	0.003	Stabilizing	0.983	D	0.651	neutral	None	None	None	None	N
E/V	0.3667	ambiguous	0.3995	ambiguous	-0.136	Destabilizing	0.957	D	0.665	neutral	N	0.486659959	None	None	N
E/W	0.9619	likely_pathogenic	0.9661	pathogenic	-0.302	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
E/Y	0.8292	likely_pathogenic	0.8481	pathogenic	-0.207	Destabilizing	0.997	D	0.765	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.