TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14954	45085;45086;45087	chr2:178622723;178622722;178622721	chr2:179487450;179487449;179487448
N2AB	13313	40162;40163;40164	chr2:178622723;178622722;178622721	chr2:179487450;179487449;179487448
N2A	12386	37381;37382;37383	chr2:178622723;178622722;178622721	chr2:179487450;179487449;179487448
N2B	5889	17890;17891;17892	chr2:178622723;178622722;178622721	chr2:179487450;179487449;179487448
Novex-1	6014	18265;18266;18267	chr2:178622723;178622722;178622721	chr2:179487450;179487449;179487448
Novex-2	6081	18466;18467;18468	chr2:178622723;178622722;178622721	chr2:179487450;179487449;179487448
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-101
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5492
• 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
R/K	rs2058479369	None	None	N	0.189	0.136	0.1749357433	gnomAD-4.0.0	6.87264E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01921E-07	0	0
R/T	None	None	0.014	N	0.357	0.154	0.198526703765	gnomAD-4.0.0	6.87264E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01921E-07	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	0.2681	likely_benign	0.2921	benign	0.038	Stabilizing	0.002	N	0.292	neutral	None	None	None	None	I
R/C	0.3567	ambiguous	0.4475	ambiguous	-0.276	Destabilizing	0.497	N	0.402	neutral	None	None	None	None	I
R/D	0.589	likely_pathogenic	0.6174	pathogenic	-0.373	Destabilizing	0.004	N	0.398	neutral	None	None	None	None	I
R/E	0.2397	likely_benign	0.2505	benign	-0.334	Destabilizing	None	N	0.183	neutral	None	None	None	None	I
R/F	0.5907	likely_pathogenic	0.6283	pathogenic	-0.27	Destabilizing	0.085	N	0.438	neutral	None	None	None	None	I
R/G	0.1947	likely_benign	0.207	benign	-0.098	Destabilizing	0.014	N	0.395	neutral	N	0.509303387	None	None	I
R/H	0.1622	likely_benign	0.1896	benign	-0.574	Destabilizing	0.245	N	0.296	neutral	None	None	None	None	I
R/I	0.2851	likely_benign	0.3083	benign	0.352	Stabilizing	None	N	0.275	neutral	N	0.488408615	None	None	I
R/K	0.0558	likely_benign	0.0557	benign	-0.205	Destabilizing	None	N	0.189	neutral	N	0.405197741	None	None	I
R/L	0.2116	likely_benign	0.2368	benign	0.352	Stabilizing	0.004	N	0.34	neutral	None	None	None	None	I
R/M	0.2149	likely_benign	0.2332	benign	-0.104	Destabilizing	0.245	N	0.382	neutral	None	None	None	None	I
R/N	0.4219	ambiguous	0.4358	ambiguous	-0.132	Destabilizing	0.018	N	0.296	neutral	None	None	None	None	I
R/P	0.3988	ambiguous	0.4165	ambiguous	0.265	Stabilizing	None	N	0.24	neutral	None	None	None	None	I
R/Q	0.1071	likely_benign	0.1148	benign	-0.16	Destabilizing	0.009	N	0.295	neutral	None	None	None	None	I
R/S	0.3449	ambiguous	0.3661	ambiguous	-0.281	Destabilizing	0.003	N	0.316	neutral	N	0.486145813	None	None	I
R/T	0.1831	likely_benign	0.1927	benign	-0.139	Destabilizing	0.014	N	0.357	neutral	N	0.439287755	None	None	I
R/V	0.3195	likely_benign	0.3463	ambiguous	0.265	Stabilizing	0.004	N	0.408	neutral	None	None	None	None	I
R/W	0.2629	likely_benign	0.2905	benign	-0.46	Destabilizing	0.788	D	0.398	neutral	None	None	None	None	I
R/Y	0.5091	ambiguous	0.5419	ambiguous	-0.061	Destabilizing	0.085	N	0.428	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.