TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32663	98212;98213;98214	chr2:178540179;178540178;178540177	chr2:179404906;179404905;179404904
N2AB	31022	93289;93290;93291	chr2:178540179;178540178;178540177	chr2:179404906;179404905;179404904
N2A	30095	90508;90509;90510	chr2:178540179;178540178;178540177	chr2:179404906;179404905;179404904
N2B	23598	71017;71018;71019	chr2:178540179;178540178;178540177	chr2:179404906;179404905;179404904
Novex-1	23723	71392;71393;71394	chr2:178540179;178540178;178540177	chr2:179404906;179404905;179404904
Novex-2	23790	71593;71594;71595	chr2:178540179;178540178;178540177	chr2:179404906;179404905;179404904
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-126
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.3297
• 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
T/I	None	None	1.0	N	0.807	0.447	0.620998120304	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85832E-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
T/A	0.2291	likely_benign	0.2629	benign	-0.592	Destabilizing	0.999	D	0.541	neutral	N	0.50693923	None	None	N
T/C	0.6678	likely_pathogenic	0.688	pathogenic	-0.255	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/D	0.8113	likely_pathogenic	0.8163	pathogenic	0.195	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
T/E	0.7413	likely_pathogenic	0.7718	pathogenic	0.132	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/F	0.6433	likely_pathogenic	0.6649	pathogenic	-1.013	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
T/G	0.4814	ambiguous	0.5151	ambiguous	-0.75	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/H	0.5456	ambiguous	0.5938	pathogenic	-1.041	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
T/I	0.4864	ambiguous	0.5275	ambiguous	-0.288	Destabilizing	1.0	D	0.807	deleterious	N	0.482350377	None	None	N
T/K	0.5237	ambiguous	0.5686	pathogenic	-0.446	Destabilizing	1.0	D	0.797	deleterious	N	0.462262947	None	None	N
T/L	0.1962	likely_benign	0.2161	benign	-0.288	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
T/M	0.1739	likely_benign	0.2062	benign	0.002	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/N	0.3257	likely_benign	0.3514	ambiguous	-0.202	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
T/P	0.1784	likely_benign	0.2178	benign	-0.36	Destabilizing	1.0	D	0.817	deleterious	N	0.510363538	None	None	N
T/Q	0.4475	ambiguous	0.5014	ambiguous	-0.429	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
T/R	0.5128	ambiguous	0.5601	ambiguous	-0.169	Destabilizing	1.0	D	0.819	deleterious	N	0.489006831	None	None	N
T/S	0.2506	likely_benign	0.2631	benign	-0.465	Destabilizing	0.999	D	0.516	neutral	N	0.477288327	None	None	N
T/V	0.3549	ambiguous	0.3876	ambiguous	-0.36	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
T/W	0.8832	likely_pathogenic	0.9021	pathogenic	-0.975	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
T/Y	0.6671	likely_pathogenic	0.7123	pathogenic	-0.718	Destabilizing	1.0	D	0.839	deleterious	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.