TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22403	67432;67433;67434	chr2:178580080;178580079;178580078	chr2:179444807;179444806;179444805
N2AB	20762	62509;62510;62511	chr2:178580080;178580079;178580078	chr2:179444807;179444806;179444805
N2A	19835	59728;59729;59730	chr2:178580080;178580079;178580078	chr2:179444807;179444806;179444805
N2B	13338	40237;40238;40239	chr2:178580080;178580079;178580078	chr2:179444807;179444806;179444805
Novex-1	13463	40612;40613;40614	chr2:178580080;178580079;178580078	chr2:179444807;179444806;179444805
Novex-2	13530	40813;40814;40815	chr2:178580080;178580079;178580078	chr2:179444807;179444806;179444805
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-50
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3918
• 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
T/I	rs767363142	-0.187	0.684	N	0.526	0.221	0.411665641125	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	1.65837E-04
T/I	rs767363142	-0.187	0.684	N	0.526	0.221	0.411665641125	gnomAD-4.0.0	1.16345E-05	None	None	None	None	N	None	0	3.5783E-04	None	0	0	None	0	0	8.99688E-07	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
T/A	0.0912	likely_benign	0.0868	benign	-0.644	Destabilizing	0.003	N	0.145	neutral	N	0.493988576	None	None	N
T/C	0.499	ambiguous	0.41	ambiguous	-0.402	Destabilizing	0.009	N	0.286	neutral	None	None	None	None	N
T/D	0.571	likely_pathogenic	0.4717	ambiguous	-0.078	Destabilizing	0.742	D	0.503	neutral	None	None	None	None	N
T/E	0.4741	ambiguous	0.4074	ambiguous	-0.12	Destabilizing	0.742	D	0.507	neutral	None	None	None	None	N
T/F	0.4529	ambiguous	0.4244	ambiguous	-0.887	Destabilizing	0.953	D	0.609	neutral	None	None	None	None	N
T/G	0.4203	ambiguous	0.3756	ambiguous	-0.846	Destabilizing	0.59	D	0.507	neutral	None	None	None	None	N
T/H	0.5042	ambiguous	0.4378	ambiguous	-1.145	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	N
T/I	0.1787	likely_benign	0.1567	benign	-0.213	Destabilizing	0.684	D	0.526	neutral	N	0.517116152	None	None	N
T/K	0.4958	ambiguous	0.4408	ambiguous	-0.63	Destabilizing	0.684	D	0.501	neutral	N	0.509072672	None	None	N
T/L	0.1238	likely_benign	0.1169	benign	-0.213	Destabilizing	0.543	D	0.461	neutral	None	None	None	None	N
T/M	0.1231	likely_benign	0.1113	benign	0.083	Stabilizing	0.984	D	0.563	neutral	None	None	None	None	N
T/N	0.1907	likely_benign	0.1589	benign	-0.452	Destabilizing	0.742	D	0.425	neutral	None	None	None	None	N
T/P	0.1629	likely_benign	0.1558	benign	-0.326	Destabilizing	0.939	D	0.564	neutral	D	0.524946201	None	None	N
T/Q	0.415	ambiguous	0.3626	ambiguous	-0.694	Destabilizing	0.91	D	0.572	neutral	None	None	None	None	N
T/R	0.4175	ambiguous	0.3934	ambiguous	-0.329	Destabilizing	0.884	D	0.575	neutral	N	0.494988654	None	None	N
T/S	0.1685	likely_benign	0.1483	benign	-0.715	Destabilizing	0.028	N	0.182	neutral	N	0.504530857	None	None	N
T/V	0.1227	likely_benign	0.1078	benign	-0.326	Destabilizing	0.59	D	0.349	neutral	None	None	None	None	N
T/W	0.7958	likely_pathogenic	0.7651	pathogenic	-0.815	Destabilizing	0.996	D	0.622	neutral	None	None	None	None	N
T/Y	0.4822	ambiguous	0.4322	ambiguous	-0.582	Destabilizing	0.984	D	0.613	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.