TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28901	86926;86927;86928	chr2:178559431;178559430;178559429	chr2:179424158;179424157;179424156
N2AB	27260	82003;82004;82005	chr2:178559431;178559430;178559429	chr2:179424158;179424157;179424156
N2A	26333	79222;79223;79224	chr2:178559431;178559430;178559429	chr2:179424158;179424157;179424156
N2B	19836	59731;59732;59733	chr2:178559431;178559430;178559429	chr2:179424158;179424157;179424156
Novex-1	19961	60106;60107;60108	chr2:178559431;178559430;178559429	chr2:179424158;179424157;179424156
Novex-2	20028	60307;60308;60309	chr2:178559431;178559430;178559429	chr2:179424158;179424157;179424156
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-98
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.6194
• 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/C	rs757848764	-0.06	1.0	N	0.73	0.335	0.613652031552	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	1.78E-05	0
R/C	rs757848764	-0.06	1.0	N	0.73	0.335	0.613652031552	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	4.78011E-04
R/C	rs757848764	-0.06	1.0	N	0.73	0.335	0.613652031552	gnomAD-4.0.0	1.23951E-05	None	None	None	None	N	None	4.0063E-05	1.66728E-05	None	0	8.91424E-05	None	0	0	6.78129E-06	1.09832E-05	4.80354E-05
R/G	rs757848764	None	1.0	N	0.611	0.275	0.543299242062	gnomAD-4.0.0	6.84262E-07	None	None	None	None	N	None	0	2.23614E-05	None	0	0	None	0	0	0	0	0
R/H	rs550229338	-0.746	1.0	N	0.76	0.331	0.254761474806	gnomAD-2.1.1	5.23E-05	None	None	None	None	N	None	0	2.9E-05	None	0	6.13908E-04	None	3.27E-05	None	0	0	0
R/H	rs550229338	-0.746	1.0	N	0.76	0.331	0.254761474806	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	5.78258E-04	None	0	0	0	0	0
R/H	rs550229338	-0.746	1.0	N	0.76	0.331	0.254761474806	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	2E-03	0	None	None	None	0	None
R/H	rs550229338	-0.746	1.0	N	0.76	0.331	0.254761474806	gnomAD-4.0.0	1.36333E-05	None	None	None	None	N	None	0	1.66656E-05	None	3.37883E-05	2.8979E-04	None	0	0	3.39066E-06	1.09827E-05	3.20133E-05

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	0.4881	ambiguous	0.4824	ambiguous	0.099	Stabilizing	0.999	D	0.624	neutral	None	None	None	None	N
R/C	0.1779	likely_benign	0.1663	benign	-0.068	Destabilizing	1.0	D	0.73	prob.delet.	N	0.516518719	None	None	N
R/D	0.7051	likely_pathogenic	0.7039	pathogenic	-0.052	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
R/E	0.5004	ambiguous	0.5059	ambiguous	0.016	Stabilizing	0.999	D	0.66	neutral	None	None	None	None	N
R/F	0.6023	likely_pathogenic	0.5742	pathogenic	-0.125	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/G	0.2857	likely_benign	0.287	benign	-0.096	Destabilizing	1.0	D	0.611	neutral	N	0.483310222	None	None	N
R/H	0.1029	likely_benign	0.0888	benign	-0.653	Destabilizing	1.0	D	0.76	deleterious	N	0.504608214	None	None	N
R/I	0.3753	ambiguous	0.3828	ambiguous	0.575	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
R/K	0.1203	likely_benign	0.1194	benign	0.042	Stabilizing	0.998	D	0.521	neutral	None	None	None	None	N
R/L	0.3219	likely_benign	0.3055	benign	0.575	Stabilizing	1.0	D	0.611	neutral	N	0.518806876	None	None	N
R/M	0.3645	ambiguous	0.3728	ambiguous	0.084	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
R/N	0.5656	likely_pathogenic	0.5456	ambiguous	0.218	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/P	0.8527	likely_pathogenic	0.8499	pathogenic	0.437	Stabilizing	1.0	D	0.683	prob.neutral	N	0.515035852	None	None	N
R/Q	0.1223	likely_benign	0.1184	benign	0.157	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
R/S	0.5126	ambiguous	0.4995	ambiguous	-0.079	Destabilizing	1.0	D	0.694	prob.neutral	N	0.461548084	None	None	N
R/T	0.3202	likely_benign	0.3257	benign	0.124	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
R/V	0.4523	ambiguous	0.4492	ambiguous	0.437	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
R/W	0.247	likely_benign	0.2417	benign	-0.226	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
R/Y	0.386	ambiguous	0.3644	ambiguous	0.198	Stabilizing	1.0	D	0.71	prob.delet.	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.