TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14988	45187;45188;45189	chr2:178621960;178621959;178621958	chr2:179486687;179486686;179486685
N2AB	13347	40264;40265;40266	chr2:178621960;178621959;178621958	chr2:179486687;179486686;179486685
N2A	12420	37483;37484;37485	chr2:178621960;178621959;178621958	chr2:179486687;179486686;179486685
N2B	5923	17992;17993;17994	chr2:178621960;178621959;178621958	chr2:179486687;179486686;179486685
Novex-1	6048	18367;18368;18369	chr2:178621960;178621959;178621958	chr2:179486687;179486686;179486685
Novex-2	6115	18568;18569;18570	chr2:178621960;178621959;178621958	chr2:179486687;179486686;179486685
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-101
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.2602
• 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
D/V	rs1478836616	None	0.997	N	0.703	0.491	0.444505407614	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
D/V	rs1478836616	None	0.997	N	0.703	0.491	0.444505407614	gnomAD-4.0.0	1.98612E-05	None	None	None	None	N	None	0	0	None	3.38776E-05	0	None	0	0	2.63023E-05	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
D/A	0.4461	ambiguous	0.5057	ambiguous	-0.684	Destabilizing	0.978	D	0.534	neutral	N	0.507513484	None	None	N
D/C	0.9318	likely_pathogenic	0.941	pathogenic	-0.265	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/E	0.2456	likely_benign	0.2698	benign	-0.673	Destabilizing	0.198	N	0.205	neutral	N	0.382366342	None	None	N
D/F	0.9263	likely_pathogenic	0.9325	pathogenic	-0.377	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
D/G	0.5279	ambiguous	0.5912	pathogenic	-1.031	Destabilizing	0.989	D	0.505	neutral	N	0.484837139	None	None	N
D/H	0.5833	likely_pathogenic	0.6247	pathogenic	-0.687	Destabilizing	1.0	D	0.621	neutral	N	0.488645922	None	None	N
D/I	0.7674	likely_pathogenic	0.8042	pathogenic	0.234	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
D/K	0.7026	likely_pathogenic	0.7637	pathogenic	-0.292	Destabilizing	0.983	D	0.479	neutral	None	None	None	None	N
D/L	0.7923	likely_pathogenic	0.8305	pathogenic	0.234	Stabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
D/M	0.8981	likely_pathogenic	0.9189	pathogenic	0.679	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
D/N	0.2055	likely_benign	0.2323	benign	-0.728	Destabilizing	0.989	D	0.471	neutral	N	0.49783388	None	None	N
D/P	0.9885	likely_pathogenic	0.9911	pathogenic	-0.048	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
D/Q	0.5721	likely_pathogenic	0.6432	pathogenic	-0.607	Destabilizing	0.995	D	0.505	neutral	None	None	None	None	N
D/R	0.7163	likely_pathogenic	0.7699	pathogenic	-0.212	Destabilizing	0.995	D	0.674	neutral	None	None	None	None	N
D/S	0.2886	likely_benign	0.3327	benign	-1.018	Destabilizing	0.983	D	0.437	neutral	None	None	None	None	N
D/T	0.4836	ambiguous	0.5322	ambiguous	-0.722	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
D/V	0.5791	likely_pathogenic	0.6189	pathogenic	-0.048	Destabilizing	0.997	D	0.703	prob.neutral	N	0.485497335	None	None	N
D/W	0.9814	likely_pathogenic	0.9845	pathogenic	-0.191	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
D/Y	0.6301	likely_pathogenic	0.6794	pathogenic	-0.113	Destabilizing	0.999	D	0.709	prob.delet.	D	0.562759758	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.