TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19445	58558;58559;58560	chr2:178594060;178594059;178594058	chr2:179458787;179458786;179458785
N2AB	17804	53635;53636;53637	chr2:178594060;178594059;178594058	chr2:179458787;179458786;179458785
N2A	16877	50854;50855;50856	chr2:178594060;178594059;178594058	chr2:179458787;179458786;179458785
N2B	10380	31363;31364;31365	chr2:178594060;178594059;178594058	chr2:179458787;179458786;179458785
Novex-1	10505	31738;31739;31740	chr2:178594060;178594059;178594058	chr2:179458787;179458786;179458785
Novex-2	10572	31939;31940;31941	chr2:178594060;178594059;178594058	chr2:179458787;179458786;179458785
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-118
• Domain position: 55
• Structural Position: 139
• Q(SASA): 0.1427
• 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	rs1418076473	1.483	0.081	N	0.562	0.167	0.307016933798	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs1418076473	1.483	0.081	N	0.562	0.167	0.307016933798	gnomAD-4.0.0	4.79018E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29684E-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
E/A	0.2555	likely_benign	0.1939	benign	-0.782	Destabilizing	0.019	N	0.581	neutral	N	0.518378093	None	None	N
E/C	0.8114	likely_pathogenic	0.7313	pathogenic	-0.601	Destabilizing	0.958	D	0.697	prob.neutral	None	None	None	None	N
E/D	0.2959	likely_benign	0.2871	benign	-1.426	Destabilizing	0.042	N	0.482	neutral	N	0.500659124	None	None	N
E/F	0.7888	likely_pathogenic	0.7107	pathogenic	-0.245	Destabilizing	0.667	D	0.697	prob.neutral	None	None	None	None	N
E/G	0.2296	likely_benign	0.1691	benign	-1.193	Destabilizing	None	N	0.421	neutral	N	0.451366454	None	None	N
E/H	0.4552	ambiguous	0.3748	ambiguous	-0.774	Destabilizing	0.667	D	0.643	neutral	None	None	None	None	N
E/I	0.4173	ambiguous	0.33	benign	0.356	Stabilizing	0.124	N	0.7	prob.neutral	None	None	None	None	N
E/K	0.2052	likely_benign	0.1621	benign	-1.178	Destabilizing	0.081	N	0.562	neutral	N	0.456425557	None	None	N
E/L	0.4603	ambiguous	0.3649	ambiguous	0.356	Stabilizing	0.055	N	0.641	neutral	None	None	None	None	N
E/M	0.5293	ambiguous	0.4277	ambiguous	0.877	Stabilizing	0.667	D	0.69	prob.neutral	None	None	None	None	N
E/N	0.3978	ambiguous	0.3349	benign	-1.539	Destabilizing	0.002	N	0.341	neutral	None	None	None	None	N
E/P	0.9692	likely_pathogenic	0.9455	pathogenic	-0.002	Destabilizing	0.364	N	0.641	neutral	None	None	None	None	N
E/Q	0.1257	likely_benign	0.1076	benign	-1.32	Destabilizing	0.301	N	0.593	neutral	N	0.449942302	None	None	N
E/R	0.2875	likely_benign	0.2175	benign	-0.967	Destabilizing	0.22	N	0.617	neutral	None	None	None	None	N
E/S	0.2672	likely_benign	0.2118	benign	-1.937	Destabilizing	0.005	N	0.303	neutral	None	None	None	None	N
E/T	0.2556	likely_benign	0.1919	benign	-1.6	Destabilizing	None	N	0.4	neutral	None	None	None	None	N
E/V	0.2502	likely_benign	0.2036	benign	-0.002	Destabilizing	0.042	N	0.634	neutral	N	0.440994745	None	None	N
E/W	0.8686	likely_pathogenic	0.8057	pathogenic	-0.163	Destabilizing	0.958	D	0.703	prob.neutral	None	None	None	None	N
E/Y	0.6344	likely_pathogenic	0.5395	ambiguous	-0.072	Destabilizing	0.667	D	0.688	prob.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.