TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10081	30466;30467;30468	chr2:178702646;178702645;178702644	chr2:179567373;179567372;179567371
N2AB	9764	29515;29516;29517	chr2:178702646;178702645;178702644	chr2:179567373;179567372;179567371
N2A	8837	26734;26735;26736	chr2:178702646;178702645;178702644	chr2:179567373;179567372;179567371
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-86
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3717
• 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/R	rs1306890743	None	1.0	None	0.839	0.51	0.861851441974	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/R	rs1306890743	None	1.0	None	0.839	0.51	0.861851441974	gnomAD-4.0.0	2.02986E-06	None	None	None	None	N	None	1.74782E-05	0	None	0	0	None	0	0	1.20492E-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	0.6261	likely_pathogenic	0.5391	ambiguous	-0.783	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
T/C	0.9468	likely_pathogenic	0.9396	pathogenic	-0.458	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/D	0.964	likely_pathogenic	0.9349	pathogenic	0.143	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
T/E	0.8965	likely_pathogenic	0.8539	pathogenic	0.152	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
T/F	0.9106	likely_pathogenic	0.8752	pathogenic	-0.832	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
T/G	0.8857	likely_pathogenic	0.8596	pathogenic	-1.045	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/H	0.862	likely_pathogenic	0.7755	pathogenic	-1.204	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
T/I	0.7698	likely_pathogenic	0.6942	pathogenic	-0.176	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
T/K	0.7649	likely_pathogenic	0.644	pathogenic	-0.564	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/L	0.4958	ambiguous	0.4312	ambiguous	-0.176	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
T/M	0.5	ambiguous	0.4041	ambiguous	0.009	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/N	0.7525	likely_pathogenic	0.6518	pathogenic	-0.53	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
T/P	0.7986	likely_pathogenic	0.7507	pathogenic	-0.346	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
T/Q	0.7591	likely_pathogenic	0.674	pathogenic	-0.646	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
T/R	0.7077	likely_pathogenic	0.54	ambiguous	-0.347	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
T/S	0.5833	likely_pathogenic	0.4813	ambiguous	-0.874	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
T/V	0.6234	likely_pathogenic	0.5782	pathogenic	-0.346	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
T/W	0.9699	likely_pathogenic	0.9617	pathogenic	-0.761	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/Y	0.9366	likely_pathogenic	0.9064	pathogenic	-0.524	Destabilizing	1.0	D	0.869	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.