TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5794	17605;17606;17607	chr2:178731386;178731385;178731384	chr2:179596113;179596112;179596111
N2AB	5477	16654;16655;16656	chr2:178731386;178731385;178731384	chr2:179596113;179596112;179596111
N2A	4550	13873;13874;13875	chr2:178731386;178731385;178731384	chr2:179596113;179596112;179596111
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-41
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.6601
• 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
V/I	rs879167621	None	0.001	N	0.125	0.084	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs879167621	None	0.001	N	0.125	0.084	None	gnomAD-4.0.0	1.31458E-05	None	None	None	None	N	None	4.82719E-05	0	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
V/A	0.1181	likely_benign	0.1128	benign	-0.993	Destabilizing	0.047	N	0.155	neutral	N	0.383326868	None	None	N
V/C	0.6993	likely_pathogenic	0.679	pathogenic	-0.484	Destabilizing	0.94	D	0.265	neutral	None	None	None	None	N
V/D	0.1661	likely_benign	0.1542	benign	-1.123	Destabilizing	0.351	N	0.404	neutral	N	0.444338042	None	None	N
V/E	0.1509	likely_benign	0.1407	benign	-1.199	Destabilizing	0.228	N	0.247	neutral	None	None	None	None	N
V/F	0.1413	likely_benign	0.1362	benign	-1.023	Destabilizing	0.351	N	0.379	neutral	N	0.435006482	None	None	N
V/G	0.1147	likely_benign	0.1082	benign	-1.199	Destabilizing	0.101	N	0.266	neutral	N	0.4445114	None	None	N
V/H	0.4175	ambiguous	0.4087	ambiguous	-0.86	Destabilizing	0.94	D	0.345	neutral	None	None	None	None	N
V/I	0.0769	likely_benign	0.0748	benign	-0.557	Destabilizing	0.001	N	0.125	neutral	N	0.438969507	None	None	N
V/K	0.1889	likely_benign	0.1859	benign	-0.96	Destabilizing	0.004	N	0.156	neutral	None	None	None	None	N
V/L	0.1291	likely_benign	0.1284	benign	-0.557	Destabilizing	None	N	0.063	neutral	N	0.390463484	None	None	N
V/M	0.1061	likely_benign	0.1014	benign	-0.394	Destabilizing	0.716	D	0.209	neutral	None	None	None	None	N
V/N	0.1591	likely_benign	0.1497	benign	-0.535	Destabilizing	0.418	N	0.401	neutral	None	None	None	None	N
V/P	0.2252	likely_benign	0.214	benign	-0.669	Destabilizing	0.002	N	0.172	neutral	None	None	None	None	N
V/Q	0.2035	likely_benign	0.2016	benign	-0.79	Destabilizing	0.418	N	0.421	neutral	None	None	None	None	N
V/R	0.1916	likely_benign	0.1969	benign	-0.38	Destabilizing	0.002	N	0.221	neutral	None	None	None	None	N
V/S	0.1358	likely_benign	0.1305	benign	-0.839	Destabilizing	0.004	N	0.15	neutral	None	None	None	None	N
V/T	0.1429	likely_benign	0.1361	benign	-0.827	Destabilizing	0.004	N	0.099	neutral	None	None	None	None	N
V/W	0.6302	likely_pathogenic	0.6196	pathogenic	-1.163	Destabilizing	0.983	D	0.349	neutral	None	None	None	None	N
V/Y	0.4007	ambiguous	0.3842	ambiguous	-0.897	Destabilizing	0.836	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.