TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22589	67990;67991;67992	chr2:178579265;178579264;178579263	chr2:179443992;179443991;179443990
N2AB	20948	63067;63068;63069	chr2:178579265;178579264;178579263	chr2:179443992;179443991;179443990
N2A	20021	60286;60287;60288	chr2:178579265;178579264;178579263	chr2:179443992;179443991;179443990
N2B	13524	40795;40796;40797	chr2:178579265;178579264;178579263	chr2:179443992;179443991;179443990
Novex-1	13649	41170;41171;41172	chr2:178579265;178579264;178579263	chr2:179443992;179443991;179443990
Novex-2	13716	41371;41372;41373	chr2:178579265;178579264;178579263	chr2:179443992;179443991;179443990
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-127
• Domain position: 30
• Structural Position: 55
• Q(SASA): 0.6531
• 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
D/V	None	None	0.022	N	0.255	0.318	0.48300943003	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
D/A	0.0979	likely_benign	0.0983	benign	-0.222	Destabilizing	0.005	N	0.235	neutral	N	0.479993063	None	None	N
D/C	0.4197	ambiguous	0.4233	ambiguous	0.02	Stabilizing	0.998	D	0.379	neutral	None	None	None	None	N
D/E	0.0829	likely_benign	0.0854	benign	-0.249	Destabilizing	0.625	D	0.312	neutral	N	0.447629929	None	None	N
D/F	0.2803	likely_benign	0.2818	benign	-0.221	Destabilizing	0.949	D	0.418	neutral	None	None	None	None	N
D/G	0.1196	likely_benign	0.119	benign	-0.403	Destabilizing	0.669	D	0.329	neutral	N	0.431913902	None	None	N
D/H	0.1746	likely_benign	0.1835	benign	-0.026	Destabilizing	0.997	D	0.342	neutral	N	0.489017978	None	None	N
D/I	0.1144	likely_benign	0.1173	benign	0.202	Stabilizing	0.728	D	0.393	neutral	None	None	None	None	N
D/K	0.1957	likely_benign	0.2059	benign	0.292	Stabilizing	0.842	D	0.35	neutral	None	None	None	None	N
D/L	0.1588	likely_benign	0.1604	benign	0.202	Stabilizing	0.525	D	0.399	neutral	None	None	None	None	N
D/M	0.2637	likely_benign	0.2644	benign	0.275	Stabilizing	0.325	N	0.405	neutral	None	None	None	None	N
D/N	0.0846	likely_benign	0.0843	benign	0.066	Stabilizing	0.891	D	0.339	neutral	N	0.474760602	None	None	N
D/P	0.6427	likely_pathogenic	0.6553	pathogenic	0.082	Stabilizing	0.974	D	0.37	neutral	None	None	None	None	N
D/Q	0.169	likely_benign	0.1728	benign	0.09	Stabilizing	0.974	D	0.332	neutral	None	None	None	None	N
D/R	0.2665	likely_benign	0.2806	benign	0.455	Stabilizing	0.974	D	0.41	neutral	None	None	None	None	N
D/S	0.1003	likely_benign	0.1023	benign	-0.053	Destabilizing	0.525	D	0.281	neutral	None	None	None	None	N
D/T	0.1196	likely_benign	0.1184	benign	0.084	Stabilizing	0.067	N	0.249	neutral	None	None	None	None	N
D/V	0.0739	likely_benign	0.076	benign	0.082	Stabilizing	0.022	N	0.255	neutral	N	0.435242209	None	None	N
D/W	0.7296	likely_pathogenic	0.7452	pathogenic	-0.122	Destabilizing	0.998	D	0.412	neutral	None	None	None	None	N
D/Y	0.1156	likely_benign	0.1144	benign	0.004	Stabilizing	0.989	D	0.405	neutral	N	0.490163008	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.