TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15180	45763;45764;45765	chr2:178621180;178621179;178621178	chr2:179485907;179485906;179485905
N2AB	13539	40840;40841;40842	chr2:178621180;178621179;178621178	chr2:179485907;179485906;179485905
N2A	12612	38059;38060;38061	chr2:178621180;178621179;178621178	chr2:179485907;179485906;179485905
N2B	6115	18568;18569;18570	chr2:178621180;178621179;178621178	chr2:179485907;179485906;179485905
Novex-1	6240	18943;18944;18945	chr2:178621180;178621179;178621178	chr2:179485907;179485906;179485905
Novex-2	6307	19144;19145;19146	chr2:178621180;178621179;178621178	chr2:179485907;179485906;179485905
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-103
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.8605
• 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
D/Y	None	None	0.989	N	0.435	0.291	0.264081493735	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1954	likely_benign	0.1639	benign	-0.304	Destabilizing	0.051	N	0.23	neutral	N	0.456917497	None	None	N
D/C	0.7616	likely_pathogenic	0.6795	pathogenic	0.133	Stabilizing	0.998	D	0.439	neutral	None	None	None	None	N
D/E	0.1896	likely_benign	0.1412	benign	-0.334	Destabilizing	0.012	N	0.25	neutral	N	0.453875368	None	None	N
D/F	0.6744	likely_pathogenic	0.6338	pathogenic	-0.35	Destabilizing	0.991	D	0.433	neutral	None	None	None	None	N
D/G	0.1416	likely_benign	0.1293	benign	-0.506	Destabilizing	0.454	N	0.36	neutral	N	0.455886189	None	None	N
D/H	0.34	ambiguous	0.3008	benign	-0.343	Destabilizing	0.966	D	0.369	neutral	N	0.446495073	None	None	N
D/I	0.5909	likely_pathogenic	0.5143	ambiguous	0.179	Stabilizing	0.974	D	0.453	neutral	None	None	None	None	N
D/K	0.4171	ambiguous	0.3692	ambiguous	0.291	Stabilizing	0.728	D	0.377	neutral	None	None	None	None	N
D/L	0.5403	ambiguous	0.488	ambiguous	0.179	Stabilizing	0.842	D	0.435	neutral	None	None	None	None	N
D/M	0.7256	likely_pathogenic	0.6288	pathogenic	0.429	Stabilizing	0.998	D	0.423	neutral	None	None	None	None	N
D/N	0.0824	likely_benign	0.0701	benign	0.048	Stabilizing	0.005	N	0.117	neutral	N	0.379024742	None	None	N
D/P	0.9177	likely_pathogenic	0.8798	pathogenic	0.04	Stabilizing	0.974	D	0.383	neutral	None	None	None	None	N
D/Q	0.3835	ambiguous	0.3181	benign	0.067	Stabilizing	0.904	D	0.355	neutral	None	None	None	None	N
D/R	0.4664	ambiguous	0.4445	ambiguous	0.371	Stabilizing	0.949	D	0.399	neutral	None	None	None	None	N
D/S	0.1488	likely_benign	0.1163	benign	-0.075	Destabilizing	0.525	D	0.353	neutral	None	None	None	None	N
D/T	0.3339	likely_benign	0.2481	benign	0.078	Stabilizing	0.842	D	0.379	neutral	None	None	None	None	N
D/V	0.356	ambiguous	0.3044	benign	0.04	Stabilizing	0.801	D	0.441	neutral	D	0.532264452	None	None	N
D/W	0.9161	likely_pathogenic	0.9069	pathogenic	-0.251	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	N
D/Y	0.2537	likely_benign	0.256	benign	-0.123	Destabilizing	0.989	D	0.435	neutral	N	0.457358743	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.