TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30964	93115;93116;93117	chr2:178548736;178548735;178548734	chr2:179413463;179413462;179413461
N2AB	29323	88192;88193;88194	chr2:178548736;178548735;178548734	chr2:179413463;179413462;179413461
N2A	28396	85411;85412;85413	chr2:178548736;178548735;178548734	chr2:179413463;179413462;179413461
N2B	21899	65920;65921;65922	chr2:178548736;178548735;178548734	chr2:179413463;179413462;179413461
Novex-1	22024	66295;66296;66297	chr2:178548736;178548735;178548734	chr2:179413463;179413462;179413461
Novex-2	22091	66496;66497;66498	chr2:178548736;178548735;178548734	chr2:179413463;179413462;179413461
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-150
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.4459
• 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/A	rs752684712	-0.166	0.005	N	0.243	0.091	0.220303561663	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	2.60764E-04	None	0	0	None	0	None	0	0	0
S/A	rs752684712	-0.166	0.005	N	0.243	0.091	0.220303561663	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
S/A	rs752684712	-0.166	0.005	N	0.243	0.091	0.220303561663	gnomAD-4.0.0	1.15302E-05	None	None	None	None	N	None	0	1.52511E-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
S/A	0.0764	likely_benign	0.0777	benign	-0.345	Destabilizing	0.005	N	0.243	neutral	N	0.483652231	None	None	N
S/C	0.0963	likely_benign	0.0949	benign	-0.276	Destabilizing	0.997	D	0.397	neutral	D	0.539526944	None	None	N
S/D	0.4202	ambiguous	0.4185	ambiguous	0.165	Stabilizing	0.915	D	0.364	neutral	None	None	None	None	N
S/E	0.549	ambiguous	0.5416	ambiguous	0.1	Stabilizing	0.842	D	0.358	neutral	None	None	None	None	N
S/F	0.2271	likely_benign	0.2305	benign	-0.809	Destabilizing	0.966	D	0.482	neutral	N	0.520767824	None	None	N
S/G	0.0772	likely_benign	0.0742	benign	-0.504	Destabilizing	0.002	N	0.199	neutral	None	None	None	None	N
S/H	0.3727	ambiguous	0.372	ambiguous	-0.985	Destabilizing	0.998	D	0.385	neutral	None	None	None	None	N
S/I	0.1515	likely_benign	0.1473	benign	-0.052	Destabilizing	0.949	D	0.493	neutral	None	None	None	None	N
S/K	0.6834	likely_pathogenic	0.6987	pathogenic	-0.547	Destabilizing	0.842	D	0.363	neutral	None	None	None	None	N
S/L	0.1102	likely_benign	0.111	benign	-0.052	Destabilizing	0.842	D	0.437	neutral	None	None	None	None	N
S/M	0.1897	likely_benign	0.1855	benign	0.038	Stabilizing	0.998	D	0.383	neutral	None	None	None	None	N
S/N	0.1409	likely_benign	0.1367	benign	-0.295	Destabilizing	0.915	D	0.442	neutral	None	None	None	None	N
S/P	0.6846	likely_pathogenic	0.659	pathogenic	-0.118	Destabilizing	0.966	D	0.385	neutral	N	0.509550753	None	None	N
S/Q	0.5025	ambiguous	0.4974	ambiguous	-0.463	Destabilizing	0.974	D	0.399	neutral	None	None	None	None	N
S/R	0.6005	likely_pathogenic	0.6143	pathogenic	-0.387	Destabilizing	0.974	D	0.39	neutral	None	None	None	None	N
S/T	0.0744	likely_benign	0.0731	benign	-0.349	Destabilizing	0.801	D	0.428	neutral	N	0.452753321	None	None	N
S/V	0.1466	likely_benign	0.143	benign	-0.118	Destabilizing	0.728	D	0.445	neutral	None	None	None	None	N
S/W	0.4303	ambiguous	0.4157	ambiguous	-0.856	Destabilizing	0.998	D	0.531	neutral	None	None	None	None	N
S/Y	0.2157	likely_benign	0.2095	benign	-0.567	Destabilizing	0.989	D	0.479	neutral	D	0.539353585	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.