TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7411	22456;22457;22458	chr2:178722668;178722667;178722666	chr2:179587395;179587394;179587393
N2AB	7094	21505;21506;21507	chr2:178722668;178722667;178722666	chr2:179587395;179587394;179587393
N2A	6167	18724;18725;18726	chr2:178722668;178722667;178722666	chr2:179587395;179587394;179587393
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-58
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.5616
• 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
R/G	rs780911294	-0.907	0.086	N	0.23	0.138	0.325533332567	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	2.96E-05	None	0	0	None	0	None	0	0	0
R/G	rs780911294	-0.907	0.086	N	0.23	0.138	0.325533332567	gnomAD-4.0.0	1.60747E-06	None	None	None	None	N	None	0	2.31911E-05	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
R/A	0.1436	likely_benign	0.2058	benign	-0.386	Destabilizing	0.051	N	0.178	neutral	None	None	None	None	N
R/C	0.1025	likely_benign	0.1348	benign	-0.415	Destabilizing	0.968	D	0.265	neutral	None	None	None	None	N
R/D	0.2723	likely_benign	0.3942	ambiguous	0.101	Stabilizing	0.223	N	0.231	neutral	None	None	None	None	N
R/E	0.1614	likely_benign	0.22	benign	0.209	Stabilizing	0.365	N	0.163	neutral	None	None	None	None	N
R/F	0.2244	likely_benign	0.3195	benign	-0.311	Destabilizing	0.908	D	0.365	neutral	None	None	None	None	N
R/G	0.1053	likely_benign	0.1603	benign	-0.666	Destabilizing	0.086	N	0.23	neutral	N	0.491033124	None	None	N
R/H	0.0621	likely_benign	0.0702	benign	-1.005	Destabilizing	0.908	D	0.274	neutral	None	None	None	None	N
R/I	0.0992	likely_benign	0.1222	benign	0.347	Stabilizing	0.178	N	0.274	neutral	N	0.418188803	None	None	N
R/K	0.0753	likely_benign	0.0889	benign	-0.387	Destabilizing	0.159	N	0.159	neutral	N	0.399429684	None	None	N
R/L	0.1031	likely_benign	0.1308	benign	0.347	Stabilizing	0.111	N	0.232	neutral	None	None	None	None	N
R/M	0.1235	likely_benign	0.1583	benign	-0.088	Destabilizing	0.908	D	0.265	neutral	None	None	None	None	N
R/N	0.1859	likely_benign	0.2666	benign	0.034	Stabilizing	0.008	N	0.131	neutral	None	None	None	None	N
R/P	0.461	ambiguous	0.6622	pathogenic	0.124	Stabilizing	0.738	D	0.357	neutral	None	None	None	None	N
R/Q	0.0708	likely_benign	0.0817	benign	-0.103	Destabilizing	0.738	D	0.226	neutral	None	None	None	None	N
R/S	0.1407	likely_benign	0.2022	benign	-0.596	Destabilizing	0.002	N	0.132	neutral	N	0.421037108	None	None	N
R/T	0.0759	likely_benign	0.0909	benign	-0.317	Destabilizing	0.002	N	0.115	neutral	N	0.335108847	None	None	N
R/V	0.1311	likely_benign	0.1656	benign	0.124	Stabilizing	0.008	N	0.197	neutral	None	None	None	None	N
R/W	0.0997	likely_benign	0.1317	benign	-0.102	Destabilizing	0.991	D	0.257	neutral	None	None	None	None	N
R/Y	0.1573	likely_benign	0.226	benign	0.23	Stabilizing	0.968	D	0.349	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.