TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32955	99088;99089;99090	chr2:178539072;178539071;178539070	chr2:179403799;179403798;179403797
N2AB	31314	94165;94166;94167	chr2:178539072;178539071;178539070	chr2:179403799;179403798;179403797
N2A	30387	91384;91385;91386	chr2:178539072;178539071;178539070	chr2:179403799;179403798;179403797
N2B	23890	71893;71894;71895	chr2:178539072;178539071;178539070	chr2:179403799;179403798;179403797
Novex-1	24015	72268;72269;72270	chr2:178539072;178539071;178539070	chr2:179403799;179403798;179403797
Novex-2	24082	72469;72470;72471	chr2:178539072;178539071;178539070	chr2:179403799;179403798;179403797
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: Fn3-128
• Domain position: 60
• Structural Position: 89
• Q(SASA): 0.3373
• 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/A	None	None	0.999	N	0.509	0.403	0.351830644314	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	5.50964E-04	None	0	0	0	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	0.223	likely_benign	0.2295	benign	-1.042	Destabilizing	0.999	D	0.509	neutral	N	0.521444536	None	None	N
T/C	0.7051	likely_pathogenic	0.7223	pathogenic	-0.544	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
T/D	0.9157	likely_pathogenic	0.9146	pathogenic	-0.155	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/E	0.868	likely_pathogenic	0.853	pathogenic	-0.032	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/F	0.832	likely_pathogenic	0.8551	pathogenic	-0.898	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/G	0.5779	likely_pathogenic	0.5994	pathogenic	-1.4	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/H	0.7983	likely_pathogenic	0.8129	pathogenic	-1.387	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/I	0.7423	likely_pathogenic	0.737	pathogenic	-0.135	Destabilizing	1.0	D	0.743	deleterious	N	0.485714058	None	None	N
T/K	0.7327	likely_pathogenic	0.7119	pathogenic	-0.324	Destabilizing	1.0	D	0.745	deleterious	N	0.514171847	None	None	N
T/L	0.2152	likely_benign	0.2377	benign	-0.135	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
T/M	0.2196	likely_benign	0.2207	benign	-0.098	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/N	0.4426	ambiguous	0.4615	ambiguous	-0.659	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/P	0.378	ambiguous	0.4152	ambiguous	-0.405	Destabilizing	1.0	D	0.745	deleterious	N	0.514633207	None	None	N
T/Q	0.6465	likely_pathogenic	0.6336	pathogenic	-0.564	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
T/R	0.6657	likely_pathogenic	0.6368	pathogenic	-0.348	Destabilizing	1.0	D	0.75	deleterious	N	0.51016875	None	None	N
T/S	0.3642	ambiguous	0.3923	ambiguous	-1.065	Destabilizing	0.999	D	0.493	neutral	N	0.46973617	None	None	N
T/V	0.4675	ambiguous	0.4705	ambiguous	-0.405	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
T/W	0.962	likely_pathogenic	0.9673	pathogenic	-0.876	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.8582	likely_pathogenic	0.8764	pathogenic	-0.567	Destabilizing	1.0	D	0.765	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.