TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35623	107092;107093;107094	chr2:178528884;178528883;178528882	chr2:179393611;179393610;179393609
N2AB	33982	102169;102170;102171	chr2:178528884;178528883;178528882	chr2:179393611;179393610;179393609
N2A	33055	99388;99389;99390	chr2:178528884;178528883;178528882	chr2:179393611;179393610;179393609
N2B	26558	79897;79898;79899	chr2:178528884;178528883;178528882	chr2:179393611;179393610;179393609
Novex-1	26683	80272;80273;80274	chr2:178528884;178528883;178528882	chr2:179393611;179393610;179393609
Novex-2	26750	80473;80474;80475	chr2:178528884;178528883;178528882	chr2:179393611;179393610;179393609
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-167
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4436
• 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
R/I	rs777105439	0.369	0.033	N	0.53	0.088	0.215109475489	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	1.11297E-04	None	0	None	0	0	0
R/S	None	None	None	N	0.159	0.056	0.0954503805726	gnomAD-4.0.0	6.84143E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.994E-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	0.3494	ambiguous	0.2913	benign	-0.226	Destabilizing	0.002	N	0.275	neutral	None	None	None	None	N
R/C	0.2853	likely_benign	0.2451	benign	-0.302	Destabilizing	0.497	N	0.443	neutral	None	None	None	None	N
R/D	0.5771	likely_pathogenic	0.5164	ambiguous	0.092	Stabilizing	0.018	N	0.367	neutral	None	None	None	None	N
R/E	0.2995	likely_benign	0.2626	benign	0.202	Stabilizing	0.004	N	0.231	neutral	None	None	None	None	N
R/F	0.5738	likely_pathogenic	0.5299	ambiguous	-0.168	Destabilizing	0.497	N	0.547	neutral	None	None	None	None	N
R/G	0.2127	likely_benign	0.1755	benign	-0.506	Destabilizing	0.006	N	0.335	neutral	N	0.427752436	None	None	N
R/H	0.1294	likely_benign	0.1205	benign	-0.904	Destabilizing	0.245	N	0.387	neutral	None	None	None	None	N
R/I	0.2012	likely_benign	0.1941	benign	0.504	Stabilizing	0.033	N	0.53	neutral	N	0.428099153	None	None	N
R/K	0.0743	likely_benign	0.0685	benign	-0.273	Destabilizing	None	N	0.091	neutral	N	0.389714123	None	None	N
R/L	0.241	likely_benign	0.2088	benign	0.504	Stabilizing	0.008	N	0.333	neutral	None	None	None	None	N
R/M	0.2123	likely_benign	0.1866	benign	0.009	Stabilizing	0.497	N	0.437	neutral	None	None	None	None	N
R/N	0.4154	ambiguous	0.3619	ambiguous	0.072	Stabilizing	0.018	N	0.282	neutral	None	None	None	None	N
R/P	0.5316	ambiguous	0.36	ambiguous	0.283	Stabilizing	0.037	N	0.439	neutral	None	None	None	None	N
R/Q	0.1152	likely_benign	0.1045	benign	-0.021	Destabilizing	0.009	N	0.331	neutral	None	None	None	None	N
R/S	0.3353	likely_benign	0.2765	benign	-0.474	Destabilizing	None	N	0.159	neutral	N	0.406219584	None	None	N
R/T	0.175	likely_benign	0.1494	benign	-0.194	Destabilizing	None	N	0.159	neutral	N	0.406392942	None	None	N
R/V	0.3114	likely_benign	0.2782	benign	0.283	Stabilizing	0.018	N	0.375	neutral	None	None	None	None	N
R/W	0.2499	likely_benign	0.2298	benign	-0.018	Destabilizing	0.788	D	0.437	neutral	None	None	None	None	N
R/Y	0.4168	ambiguous	0.3754	ambiguous	0.334	Stabilizing	0.085	N	0.563	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.