TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16109	48550;48551;48552	chr2:178615776;178615775;178615774	chr2:179480503;179480502;179480501
N2AB	14468	43627;43628;43629	chr2:178615776;178615775;178615774	chr2:179480503;179480502;179480501
N2A	13541	40846;40847;40848	chr2:178615776;178615775;178615774	chr2:179480503;179480502;179480501
N2B	7044	21355;21356;21357	chr2:178615776;178615775;178615774	chr2:179480503;179480502;179480501
Novex-1	7169	21730;21731;21732	chr2:178615776;178615775;178615774	chr2:179480503;179480502;179480501
Novex-2	7236	21931;21932;21933	chr2:178615776;178615775;178615774	chr2:179480503;179480502;179480501
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-4
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.1028
• 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/M	None	None	0.317	D	0.599	0.223	0.430923071578	gnomAD-4.0.0	1.59682E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86761E-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
V/A	0.2965	likely_benign	0.3565	ambiguous	-1.353	Destabilizing	0.027	N	0.526	neutral	N	0.509133154	None	None	N
V/C	0.676	likely_pathogenic	0.735	pathogenic	-0.706	Destabilizing	0.935	D	0.521	neutral	None	None	None	None	N
V/D	0.7638	likely_pathogenic	0.8092	pathogenic	-1.638	Destabilizing	0.38	N	0.622	neutral	None	None	None	None	N
V/E	0.6587	likely_pathogenic	0.6828	pathogenic	-1.356	Destabilizing	0.484	N	0.6	neutral	D	0.538287649	None	None	N
V/F	0.3624	ambiguous	0.4148	ambiguous	-0.668	Destabilizing	0.38	N	0.601	neutral	None	None	None	None	N
V/G	0.4532	ambiguous	0.5127	ambiguous	-1.938	Destabilizing	None	N	0.483	neutral	N	0.489627273	None	None	N
V/H	0.7948	likely_pathogenic	0.8523	pathogenic	-1.907	Destabilizing	0.935	D	0.582	neutral	None	None	None	None	N
V/I	0.0887	likely_benign	0.0977	benign	0.299	Stabilizing	None	N	0.152	neutral	None	None	None	None	N
V/K	0.6773	likely_pathogenic	0.7344	pathogenic	-0.718	Destabilizing	0.38	N	0.605	neutral	None	None	None	None	N
V/L	0.225	likely_benign	0.2735	benign	0.299	Stabilizing	None	N	0.205	neutral	N	0.477660745	None	None	N
V/M	0.2342	likely_benign	0.291	benign	0.11	Stabilizing	0.317	N	0.599	neutral	D	0.581187225	None	None	N
V/N	0.5675	likely_pathogenic	0.6513	pathogenic	-1.168	Destabilizing	0.38	N	0.627	neutral	None	None	None	None	N
V/P	0.7497	likely_pathogenic	0.8148	pathogenic	-0.226	Destabilizing	0.555	D	0.607	neutral	None	None	None	None	N
V/Q	0.5889	likely_pathogenic	0.6596	pathogenic	-0.844	Destabilizing	0.555	D	0.569	neutral	None	None	None	None	N
V/R	0.6268	likely_pathogenic	0.6917	pathogenic	-1.016	Destabilizing	0.555	D	0.629	neutral	None	None	None	None	N
V/S	0.4066	ambiguous	0.4903	ambiguous	-1.806	Destabilizing	0.081	N	0.605	neutral	None	None	None	None	N
V/T	0.3375	likely_benign	0.4049	ambiguous	-1.355	Destabilizing	0.149	N	0.585	neutral	None	None	None	None	N
V/W	0.9409	likely_pathogenic	0.9576	pathogenic	-1.201	Destabilizing	0.935	D	0.621	neutral	None	None	None	None	N
V/Y	0.8034	likely_pathogenic	0.8485	pathogenic	-0.709	Destabilizing	0.791	D	0.601	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.