TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24920	74983;74984;74985	chr2:178571374;178571373;178571372	chr2:179436101;179436100;179436099
N2AB	23279	70060;70061;70062	chr2:178571374;178571373;178571372	chr2:179436101;179436100;179436099
N2A	22352	67279;67280;67281	chr2:178571374;178571373;178571372	chr2:179436101;179436100;179436099
N2B	15855	47788;47789;47790	chr2:178571374;178571373;178571372	chr2:179436101;179436100;179436099
Novex-1	15980	48163;48164;48165	chr2:178571374;178571373;178571372	chr2:179436101;179436100;179436099
Novex-2	16047	48364;48365;48366	chr2:178571374;178571373;178571372	chr2:179436101;179436100;179436099
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-69
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3477
• 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
S/C	None	None	None	N	0.227	0.075	0.252162846088	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
S/A	0.0595	likely_benign	0.0548	benign	-0.628	Destabilizing	None	N	0.036	neutral	N	0.40353993	None	None	N
S/C	0.0575	likely_benign	0.0594	benign	-0.702	Destabilizing	None	N	0.227	neutral	N	0.471458433	None	None	N
S/D	0.5807	likely_pathogenic	0.5558	ambiguous	-1.335	Destabilizing	None	N	0.094	neutral	None	None	None	None	N
S/E	0.5896	likely_pathogenic	0.553	ambiguous	-1.335	Destabilizing	0.009	N	0.241	neutral	None	None	None	None	N
S/F	0.1499	likely_benign	0.1576	benign	-1.124	Destabilizing	None	N	0.259	neutral	N	0.470111639	None	None	N
S/G	0.1017	likely_benign	0.0993	benign	-0.829	Destabilizing	0.009	N	0.244	neutral	None	None	None	None	N
S/H	0.3025	likely_benign	0.3009	benign	-1.499	Destabilizing	0.245	N	0.311	neutral	None	None	None	None	N
S/I	0.0862	likely_benign	0.089	benign	-0.199	Destabilizing	0.009	N	0.295	neutral	None	None	None	None	N
S/K	0.5993	likely_pathogenic	0.5869	pathogenic	-0.725	Destabilizing	0.018	N	0.257	neutral	None	None	None	None	N
S/L	0.0791	likely_benign	0.0788	benign	-0.199	Destabilizing	0.004	N	0.289	neutral	None	None	None	None	N
S/M	0.1497	likely_benign	0.1594	benign	0.194	Stabilizing	0.245	N	0.326	neutral	None	None	None	None	N
S/N	0.1804	likely_benign	0.183	benign	-0.914	Destabilizing	0.022	N	0.269	neutral	None	None	None	None	N
S/P	0.2414	likely_benign	0.1866	benign	-0.312	Destabilizing	0.033	N	0.391	neutral	N	0.482520789	None	None	N
S/Q	0.4257	ambiguous	0.4202	ambiguous	-1.181	Destabilizing	0.085	N	0.329	neutral	None	None	None	None	N
S/R	0.4611	ambiguous	0.4518	ambiguous	-0.577	Destabilizing	0.044	N	0.429	neutral	None	None	None	None	N
S/T	0.0748	likely_benign	0.0763	benign	-0.765	Destabilizing	None	N	0.082	neutral	N	0.442962323	None	None	N
S/V	0.0868	likely_benign	0.0873	benign	-0.312	Destabilizing	None	N	0.139	neutral	None	None	None	None	N
S/W	0.3113	likely_benign	0.3178	benign	-1.191	Destabilizing	0.55	D	0.41	neutral	None	None	None	None	N
S/Y	0.151	likely_benign	0.15	benign	-0.836	Destabilizing	0.017	N	0.465	neutral	N	0.503512136	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.