TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1631	5116;5117;5118	chr2:178776973;178776972;178776971	chr2:179641700;179641699;179641698
N2AB	1631	5116;5117;5118	chr2:178776973;178776972;178776971	chr2:179641700;179641699;179641698
N2A	1631	5116;5117;5118	chr2:178776973;178776972;178776971	chr2:179641700;179641699;179641698
N2B	1585	4978;4979;4980	chr2:178776973;178776972;178776971	chr2:179641700;179641699;179641698
Novex-1	1585	4978;4979;4980	chr2:178776973;178776972;178776971	chr2:179641700;179641699;179641698
Novex-2	1585	4978;4979;4980	chr2:178776973;178776972;178776971	chr2:179641700;179641699;179641698
Novex-3	1631	5116;5117;5118	chr2:178776973;178776972;178776971	chr2:179641700;179641699;179641698

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-7
• Domain position: 76
• Structural Position: 157
• Q(SASA): 0.1587
• 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	rs1270981853	-1.404	0.999	D	0.585	0.484	0.40218521252	gnomAD-2.1.1	4E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/A	rs1270981853	-1.404	0.999	D	0.585	0.484	0.40218521252	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	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	0.6329	likely_pathogenic	0.52	ambiguous	-1.068	Destabilizing	0.999	D	0.585	neutral	D	0.556596464	None	None	N
T/C	0.9613	likely_pathogenic	0.9349	pathogenic	-0.71	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
T/D	0.9969	likely_pathogenic	0.9943	pathogenic	-1.007	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
T/E	0.9889	likely_pathogenic	0.983	pathogenic	-0.837	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/F	0.9601	likely_pathogenic	0.9433	pathogenic	-0.702	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
T/G	0.9613	likely_pathogenic	0.9358	pathogenic	-1.475	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
T/H	0.9774	likely_pathogenic	0.9634	pathogenic	-1.58	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
T/I	0.7992	likely_pathogenic	0.7343	pathogenic	-0.014	Destabilizing	1.0	D	0.861	deleterious	N	0.497234809	None	None	N
T/K	0.981	likely_pathogenic	0.9687	pathogenic	-0.569	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
T/L	0.6948	likely_pathogenic	0.6211	pathogenic	-0.014	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
T/M	0.4885	ambiguous	0.4041	ambiguous	-0.021	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
T/N	0.944	likely_pathogenic	0.9067	pathogenic	-1.097	Destabilizing	1.0	D	0.712	prob.delet.	N	0.513059186	None	None	N
T/P	0.978	likely_pathogenic	0.9637	pathogenic	-0.333	Destabilizing	1.0	D	0.865	deleterious	D	0.680099881	None	None	N
T/Q	0.9666	likely_pathogenic	0.9455	pathogenic	-0.924	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
T/R	0.9757	likely_pathogenic	0.9616	pathogenic	-0.717	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
T/S	0.8145	likely_pathogenic	0.7258	pathogenic	-1.367	Destabilizing	0.999	D	0.571	neutral	N	0.50767699	None	None	N
T/V	0.5567	ambiguous	0.4979	ambiguous	-0.333	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
T/W	0.9918	likely_pathogenic	0.9876	pathogenic	-0.793	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
T/Y	0.9778	likely_pathogenic	0.966	pathogenic	-0.444	Destabilizing	1.0	D	0.907	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.