TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2437	7534;7535;7536	chr2:178773859;178773858;178773857	chr2:179638586;179638585;179638584
N2AB	2437	7534;7535;7536	chr2:178773859;178773858;178773857	chr2:179638586;179638585;179638584
N2A	2437	7534;7535;7536	chr2:178773859;178773858;178773857	chr2:179638586;179638585;179638584
N2B	2391	7396;7397;7398	chr2:178773859;178773858;178773857	chr2:179638586;179638585;179638584
Novex-1	2391	7396;7397;7398	chr2:178773859;178773858;178773857	chr2:179638586;179638585;179638584
Novex-2	2391	7396;7397;7398	chr2:178773859;178773858;178773857	chr2:179638586;179638585;179638584
Novex-3	2437	7534;7535;7536	chr2:178773859;178773858;178773857	chr2:179638586;179638585;179638584

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-13
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.498
• 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
S/T	None	None	None	N	0.227	0.067	0.162503812791	gnomAD-4.0.0	1.59061E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85665E-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
S/A	0.0801	likely_benign	0.0823	benign	-0.51	Destabilizing	None	N	0.213	neutral	None	None	None	None	N
S/C	0.1008	likely_benign	0.1117	benign	-0.159	Destabilizing	0.422	N	0.498	neutral	D	0.640232911	None	None	N
S/D	0.3009	likely_benign	0.3123	benign	0.105	Stabilizing	0.018	N	0.377	neutral	None	None	None	None	N
S/E	0.393	ambiguous	0.4061	ambiguous	-0.003	Destabilizing	0.018	N	0.383	neutral	None	None	None	None	N
S/F	0.1765	likely_benign	0.1905	benign	-1.273	Destabilizing	0.112	N	0.5	neutral	None	None	None	None	N
S/G	0.1	likely_benign	0.1067	benign	-0.563	Destabilizing	0.006	N	0.381	neutral	D	0.597156617	None	None	N
S/H	0.2067	likely_benign	0.2048	benign	-1.206	Destabilizing	None	N	0.258	neutral	None	None	None	None	N
S/I	0.1462	likely_benign	0.1569	benign	-0.49	Destabilizing	None	N	0.325	neutral	D	0.638771867	None	None	N
S/K	0.4233	ambiguous	0.4123	ambiguous	-0.252	Destabilizing	0.018	N	0.377	neutral	None	None	None	None	N
S/L	0.1153	likely_benign	0.1222	benign	-0.49	Destabilizing	0.007	N	0.376	neutral	None	None	None	None	N
S/M	0.1635	likely_benign	0.1767	benign	-0.009	Destabilizing	0.112	N	0.515	neutral	None	None	None	None	N
S/N	0.099	likely_benign	0.1023	benign	0.054	Stabilizing	None	N	0.226	neutral	D	0.551084444	None	None	N
S/P	0.6938	likely_pathogenic	0.6931	pathogenic	-0.474	Destabilizing	0.204	N	0.541	neutral	None	None	None	None	N
S/Q	0.3326	likely_benign	0.3312	benign	-0.283	Destabilizing	0.112	N	0.501	neutral	None	None	None	None	N
S/R	0.3456	ambiguous	0.3432	ambiguous	-0.094	Destabilizing	0.026	N	0.507	neutral	D	0.636692889	None	None	N
S/T	0.0624	likely_benign	0.0661	benign	-0.088	Destabilizing	None	N	0.227	neutral	N	0.506723871	None	None	N
S/V	0.1426	likely_benign	0.1544	benign	-0.474	Destabilizing	0.007	N	0.376	neutral	None	None	None	None	N
S/W	0.3556	ambiguous	0.3787	ambiguous	-1.248	Destabilizing	0.747	D	0.513	neutral	None	None	None	None	N
S/Y	0.1648	likely_benign	0.1729	benign	-0.964	Destabilizing	0.06	N	0.488	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.