TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23120	69583;69584;69585	chr2:178576977;178576976;178576975	chr2:179441704;179441703;179441702
N2AB	21479	64660;64661;64662	chr2:178576977;178576976;178576975	chr2:179441704;179441703;179441702
N2A	20552	61879;61880;61881	chr2:178576977;178576976;178576975	chr2:179441704;179441703;179441702
N2B	14055	42388;42389;42390	chr2:178576977;178576976;178576975	chr2:179441704;179441703;179441702
Novex-1	14180	42763;42764;42765	chr2:178576977;178576976;178576975	chr2:179441704;179441703;179441702
Novex-2	14247	42964;42965;42966	chr2:178576977;178576976;178576975	chr2:179441704;179441703;179441702
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-55
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.7298
• 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
Y/C	rs1271048199	None	1.0	N	0.788	0.299	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
Y/C	rs1271048199	None	1.0	N	0.788	0.299	None	gnomAD-4.0.0	3.04497E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.61489E-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
Y/A	0.6676	likely_pathogenic	0.6915	pathogenic	-0.605	Destabilizing	0.991	D	0.653	neutral	None	None	None	None	I
Y/C	0.1505	likely_benign	0.1358	benign	0.312	Stabilizing	1.0	D	0.788	deleterious	N	0.470038885	None	None	I
Y/D	0.7357	likely_pathogenic	0.801	pathogenic	0.803	Stabilizing	0.999	D	0.754	deleterious	N	0.493014531	None	None	I
Y/E	0.8788	likely_pathogenic	0.9021	pathogenic	0.778	Stabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
Y/F	0.0654	likely_benign	0.0565	benign	-0.347	Destabilizing	0.117	N	0.408	neutral	N	0.49419922	None	None	I
Y/G	0.7331	likely_pathogenic	0.7779	pathogenic	-0.796	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I
Y/H	0.1933	likely_benign	0.2247	benign	0.186	Stabilizing	0.999	D	0.654	neutral	N	0.475354803	None	None	I
Y/I	0.4505	ambiguous	0.4373	ambiguous	-0.123	Destabilizing	0.99	D	0.657	neutral	None	None	None	None	I
Y/K	0.8174	likely_pathogenic	0.8746	pathogenic	0.332	Stabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
Y/L	0.5715	likely_pathogenic	0.575	pathogenic	-0.123	Destabilizing	0.966	D	0.622	neutral	None	None	None	None	I
Y/M	0.6292	likely_pathogenic	0.6123	pathogenic	0.041	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
Y/N	0.4025	ambiguous	0.4375	ambiguous	0.217	Stabilizing	0.999	D	0.754	deleterious	N	0.474340845	None	None	I
Y/P	0.9722	likely_pathogenic	0.9772	pathogenic	-0.264	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	I
Y/Q	0.6869	likely_pathogenic	0.7408	pathogenic	0.23	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
Y/R	0.6458	likely_pathogenic	0.737	pathogenic	0.576	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
Y/S	0.4232	ambiguous	0.4722	ambiguous	-0.18	Destabilizing	0.997	D	0.719	prob.delet.	N	0.512726265	None	None	I
Y/T	0.6913	likely_pathogenic	0.7108	pathogenic	-0.111	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
Y/V	0.4087	ambiguous	0.4015	ambiguous	-0.264	Destabilizing	0.983	D	0.661	neutral	None	None	None	None	I
Y/W	0.4147	ambiguous	0.4131	ambiguous	-0.491	Destabilizing	1.0	D	0.655	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.