TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4666	14221;14222;14223	chr2:178739237;178739236;178739235	chr2:179603964;179603963;179603962
N2AB	4349	13270;13271;13272	chr2:178739237;178739236;178739235	chr2:179603964;179603963;179603962
N2A	None	None	chr2:None	chr2:None
N2B	4303	13132;13133;13134	chr2:178739237;178739236;178739235	chr2:179603964;179603963;179603962
Novex-1	4428	13507;13508;13509	chr2:178739237;178739236;178739235	chr2:179603964;179603963;179603962
Novex-2	4495	13708;13709;13710	chr2:178739237;178739236;178739235	chr2:179603964;179603963;179603962
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-29
• Domain position: 61
• Structural Position: 144
• Q(SASA): 0.0797
• 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
V/I	rs1361124171	-1.021	0.565	D	0.545	0.19	None	gnomAD-2.1.1	4.24E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.3E-06	0
V/I	rs1361124171	-1.021	0.565	D	0.545	0.19	None	gnomAD-4.0.0	1.04332E-05	None	None	None	None	N	None	0	2.292E-05	None	0	0	None	0	0	1.1851E-05	0	1.68674E-05
V/L	None	None	0.349	D	0.549	0.209	None	gnomAD-4.0.0	1.3911E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.82322E-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
V/A	0.3133	likely_benign	0.3338	benign	-2.331	Highly Destabilizing	0.003	N	0.295	neutral	N	0.513375193	None	None	N
V/C	0.8408	likely_pathogenic	0.8408	pathogenic	-2.326	Highly Destabilizing	0.989	D	0.649	neutral	None	None	None	None	N
V/D	0.877	likely_pathogenic	0.8862	pathogenic	-3.46	Highly Destabilizing	0.923	D	0.707	prob.neutral	None	None	None	None	N
V/E	0.8146	likely_pathogenic	0.8252	pathogenic	-3.305	Highly Destabilizing	0.901	D	0.663	neutral	D	0.709504627	None	None	N
V/F	0.5864	likely_pathogenic	0.5975	pathogenic	-1.395	Destabilizing	0.961	D	0.671	neutral	None	None	None	None	N
V/G	0.4373	ambiguous	0.4633	ambiguous	-2.764	Highly Destabilizing	0.565	D	0.669	neutral	D	0.746696072	None	None	N
V/H	0.9545	likely_pathogenic	0.9578	pathogenic	-2.184	Highly Destabilizing	0.996	D	0.698	prob.neutral	None	None	None	None	N
V/I	0.1032	likely_benign	0.1013	benign	-1.134	Destabilizing	0.565	D	0.545	neutral	D	0.556922522	None	None	N
V/K	0.8908	likely_pathogenic	0.8974	pathogenic	-1.995	Destabilizing	0.923	D	0.663	neutral	None	None	None	None	N
V/L	0.4107	ambiguous	0.4217	ambiguous	-1.134	Destabilizing	0.349	N	0.549	neutral	D	0.554466029	None	None	N
V/M	0.353	ambiguous	0.3553	ambiguous	-1.39	Destabilizing	0.961	D	0.595	neutral	None	None	None	None	N
V/N	0.7699	likely_pathogenic	0.7784	pathogenic	-2.34	Highly Destabilizing	0.923	D	0.723	prob.delet.	None	None	None	None	N
V/P	0.775	likely_pathogenic	0.8314	pathogenic	-1.509	Destabilizing	0.961	D	0.687	prob.neutral	None	None	None	None	N
V/Q	0.8672	likely_pathogenic	0.8743	pathogenic	-2.321	Highly Destabilizing	0.961	D	0.675	prob.neutral	None	None	None	None	N
V/R	0.8639	likely_pathogenic	0.8736	pathogenic	-1.6	Destabilizing	0.923	D	0.724	prob.delet.	None	None	None	None	N
V/S	0.5826	likely_pathogenic	0.5967	pathogenic	-2.839	Highly Destabilizing	0.633	D	0.618	neutral	None	None	None	None	N
V/T	0.396	ambiguous	0.4115	ambiguous	-2.568	Highly Destabilizing	0.011	N	0.399	neutral	None	None	None	None	N
V/W	0.9712	likely_pathogenic	0.9715	pathogenic	-1.8	Destabilizing	0.996	D	0.691	prob.neutral	None	None	None	None	N
V/Y	0.9036	likely_pathogenic	0.9079	pathogenic	-1.551	Destabilizing	0.961	D	0.657	neutral	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.