TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4686	14281;14282;14283	chr2:178739177;178739176;178739175	chr2:179603904;179603903;179603902
N2AB	4369	13330;13331;13332	chr2:178739177;178739176;178739175	chr2:179603904;179603903;179603902
N2A	None	None	chr2:None	chr2:None
N2B	4323	13192;13193;13194	chr2:178739177;178739176;178739175	chr2:179603904;179603903;179603902
Novex-1	4448	13567;13568;13569	chr2:178739177;178739176;178739175	chr2:179603904;179603903;179603902
Novex-2	4515	13768;13769;13770	chr2:178739177;178739176;178739175	chr2:179603904;179603903;179603902
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: Ig-29
• Domain position: 81
• Structural Position: 166
• Q(SASA): 0.3215
• Predicted PPI site: I

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	rs1436112479	None	None	N	0.303	0.131	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1436112479	None	None	N	0.303	0.131	None	gnomAD-4.0.0	1.97805E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.64547E-06	0	0
T/K	None	None	None	N	0.223	0.143	None	gnomAD-4.0.0	2.93143E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.75235E-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
T/A	0.071	likely_benign	0.0667	benign	-0.786	Destabilizing	None	N	0.075	neutral	N	0.403462085	None	None	I
T/C	0.4126	ambiguous	0.4097	ambiguous	-0.513	Destabilizing	0.676	D	0.461	neutral	None	None	None	None	I
T/D	0.3487	ambiguous	0.3559	ambiguous	-0.197	Destabilizing	0.038	N	0.48	neutral	None	None	None	None	I
T/E	0.2612	likely_benign	0.2819	benign	-0.183	Destabilizing	0.038	N	0.458	neutral	None	None	None	None	I
T/F	0.2564	likely_benign	0.2887	benign	-0.76	Destabilizing	0.214	N	0.572	neutral	None	None	None	None	I
T/G	0.2571	likely_benign	0.2646	benign	-1.063	Destabilizing	0.016	N	0.492	neutral	None	None	None	None	I
T/H	0.2902	likely_benign	0.3369	benign	-1.288	Destabilizing	0.356	N	0.549	neutral	None	None	None	None	I
T/I	0.1684	likely_benign	0.1915	benign	-0.137	Destabilizing	None	N	0.303	neutral	N	0.488645922	None	None	I
T/K	0.1979	likely_benign	0.2262	benign	-0.781	Destabilizing	None	N	0.223	neutral	N	0.506972377	None	None	I
T/L	0.1326	likely_benign	0.1479	benign	-0.137	Destabilizing	0.006	N	0.451	neutral	None	None	None	None	I
T/M	0.0983	likely_benign	0.1032	benign	0.017	Stabilizing	0.007	N	0.372	neutral	None	None	None	None	I
T/N	0.1515	likely_benign	0.1611	benign	-0.721	Destabilizing	None	N	0.231	neutral	None	None	None	None	I
T/P	0.5581	ambiguous	0.6225	pathogenic	-0.32	Destabilizing	0.055	N	0.518	neutral	D	0.532285198	None	None	I
T/Q	0.2516	likely_benign	0.275	benign	-0.832	Destabilizing	0.072	N	0.513	neutral	None	None	None	None	I
T/R	0.1614	likely_benign	0.1826	benign	-0.57	Destabilizing	None	N	0.295	neutral	N	0.503108516	None	None	I
T/S	0.1257	likely_benign	0.1281	benign	-0.996	Destabilizing	0.012	N	0.333	neutral	N	0.493052711	None	None	I
T/V	0.1293	likely_benign	0.1377	benign	-0.32	Destabilizing	0.006	N	0.301	neutral	None	None	None	None	I
T/W	0.6524	likely_pathogenic	0.6889	pathogenic	-0.715	Destabilizing	0.864	D	0.553	neutral	None	None	None	None	I
T/Y	0.2968	likely_benign	0.3163	benign	-0.487	Destabilizing	0.356	N	0.553	neutral	None	None	None	None	I

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.