TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8361	25306;25307;25308	chr2:178717793;178717792;178717791	chr2:179582520;179582519;179582518
N2AB	8044	24355;24356;24357	chr2:178717793;178717792;178717791	chr2:179582520;179582519;179582518
N2A	7117	21574;21575;21576	chr2:178717793;178717792;178717791	chr2:179582520;179582519;179582518
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-69
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5617
• 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
F/L	rs1553901979	None	None	N	0.134	0.073	0.186928172975	gnomAD-4.0.0	6.87138E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01988E-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
F/A	0.0845	likely_benign	0.0967	benign	-1.453	Destabilizing	None	N	0.177	neutral	None	None	None	None	N
F/C	0.1428	likely_benign	0.1719	benign	-0.629	Destabilizing	0.003	N	0.316	neutral	N	0.475472678	None	None	N
F/D	0.4663	ambiguous	0.5504	ambiguous	0.264	Stabilizing	None	N	0.235	neutral	None	None	None	None	N
F/E	0.6034	likely_pathogenic	0.6508	pathogenic	0.289	Stabilizing	None	N	0.23	neutral	None	None	None	None	N
F/G	0.2594	likely_benign	0.3412	ambiguous	-1.704	Destabilizing	None	N	0.242	neutral	None	None	None	None	N
F/H	0.2852	likely_benign	0.3269	benign	0.002	Stabilizing	0.008	N	0.269	neutral	None	None	None	None	N
F/I	0.098	likely_benign	0.1098	benign	-0.754	Destabilizing	None	N	0.155	neutral	N	0.424121138	None	None	N
F/K	0.6242	likely_pathogenic	0.683	pathogenic	-0.533	Destabilizing	None	N	0.23	neutral	None	None	None	None	N
F/L	0.3226	likely_benign	0.3913	ambiguous	-0.754	Destabilizing	None	N	0.134	neutral	N	0.448728794	None	None	N
F/M	0.2206	likely_benign	0.2315	benign	-0.618	Destabilizing	0.001	N	0.269	neutral	None	None	None	None	N
F/N	0.1618	likely_benign	0.1951	benign	-0.566	Destabilizing	None	N	0.237	neutral	None	None	None	None	N
F/P	0.9142	likely_pathogenic	0.9559	pathogenic	-0.972	Destabilizing	None	N	0.267	neutral	None	None	None	None	N
F/Q	0.4544	ambiguous	0.5135	ambiguous	-0.614	Destabilizing	None	N	0.274	neutral	None	None	None	None	N
F/R	0.461	ambiguous	0.5258	ambiguous	0.033	Stabilizing	None	N	0.269	neutral	None	None	None	None	N
F/S	0.051	likely_benign	0.0536	benign	-1.307	Destabilizing	None	N	0.168	neutral	N	0.335558004	None	None	N
F/T	0.0666	likely_benign	0.0685	benign	-1.188	Destabilizing	None	N	0.168	neutral	None	None	None	None	N
F/V	0.0846	likely_benign	0.0914	benign	-0.972	Destabilizing	None	N	0.161	neutral	N	0.406244666	None	None	N
F/W	0.3569	ambiguous	0.4033	ambiguous	-0.233	Destabilizing	0.051	N	0.271	neutral	None	None	None	None	N
F/Y	0.1028	likely_benign	0.1067	benign	-0.356	Destabilizing	0.001	N	0.265	neutral	N	0.439935952	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.