TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3349	10270;10271;10272	chr2:178764246;178764245;178764244	chr2:179628973;179628972;179628971
N2AB	3349	10270;10271;10272	chr2:178764246;178764245;178764244	chr2:179628973;179628972;179628971
N2A	3349	10270;10271;10272	chr2:178764246;178764245;178764244	chr2:179628973;179628972;179628971
N2B	3303	10132;10133;10134	chr2:178764246;178764245;178764244	chr2:179628973;179628972;179628971
Novex-1	3303	10132;10133;10134	chr2:178764246;178764245;178764244	chr2:179628973;179628972;179628971
Novex-2	3303	10132;10133;10134	chr2:178764246;178764245;178764244	chr2:179628973;179628972;179628971
Novex-3	3349	10270;10271;10272	chr2:178764246;178764245;178764244	chr2:179628973;179628972;179628971

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-24
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2182
• 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	rs777960129	-0.815	None	N	0.101	0.064	0.180583059064	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
T/A	rs777960129	-0.815	None	N	0.101	0.064	0.180583059064	gnomAD-4.0.0	7.52495E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99313E-06	0	1.65579E-05
T/I	rs727503678	0.098	None	N	0.224	0.114	0.348101942276	gnomAD-2.1.1	1.52137E-04	None	None	None	None	N	None	0	1.21414E-03	None	0	0	None	0	None	0	0	0
T/I	rs727503678	0.098	None	N	0.224	0.114	0.348101942276	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	0	7.19707E-04	0	0	0	None	0	0	0	0	0
T/I	rs727503678	0.098	None	N	0.224	0.114	0.348101942276	gnomAD-4.0.0	3.59354E-05	None	None	None	None	N	None	0	9.49937E-04	None	0	0	None	0	0	0	0	1.60051E-05
T/N	rs727503678	-0.738	0.029	N	0.272	0.107	0.316494231283	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
T/N	rs727503678	-0.738	0.029	N	0.272	0.107	0.316494231283	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs727503678	-0.738	0.029	N	0.272	0.107	0.316494231283	gnomAD-4.0.0	6.57013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46977E-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
T/A	0.0873	likely_benign	0.0843	benign	-0.725	Destabilizing	None	N	0.101	neutral	N	0.501573347	None	None	N
T/C	0.5036	ambiguous	0.3978	ambiguous	-0.527	Destabilizing	0.356	N	0.378	neutral	None	None	None	None	N
T/D	0.3715	ambiguous	0.3232	benign	-0.348	Destabilizing	0.038	N	0.387	neutral	None	None	None	None	N
T/E	0.246	likely_benign	0.2462	benign	-0.34	Destabilizing	0.038	N	0.325	neutral	None	None	None	None	N
T/F	0.1898	likely_benign	0.1698	benign	-0.666	Destabilizing	0.214	N	0.434	neutral	None	None	None	None	N
T/G	0.3399	likely_benign	0.3035	benign	-0.997	Destabilizing	0.016	N	0.361	neutral	None	None	None	None	N
T/H	0.2245	likely_benign	0.1977	benign	-1.224	Destabilizing	0.676	D	0.388	neutral	None	None	None	None	N
T/I	0.1203	likely_benign	0.1217	benign	-0.091	Destabilizing	None	N	0.224	neutral	N	0.512147944	None	None	N
T/K	0.2158	likely_benign	0.2068	benign	-0.892	Destabilizing	0.038	N	0.328	neutral	None	None	None	None	N
T/L	0.0901	likely_benign	0.084	benign	-0.091	Destabilizing	0.007	N	0.291	neutral	None	None	None	None	N
T/M	0.0994	likely_benign	0.085	benign	0.067	Stabilizing	0.007	N	0.288	neutral	None	None	None	None	N
T/N	0.1398	likely_benign	0.1171	benign	-0.846	Destabilizing	0.029	N	0.272	neutral	N	0.514095914	None	None	N
T/P	0.3268	likely_benign	0.3384	benign	-0.27	Destabilizing	0.055	N	0.428	neutral	D	0.587072243	None	None	N
T/Q	0.2027	likely_benign	0.1972	benign	-0.97	Destabilizing	0.214	N	0.409	neutral	None	None	None	None	N
T/R	0.1731	likely_benign	0.16	benign	-0.634	Destabilizing	0.214	N	0.415	neutral	None	None	None	None	N
T/S	0.1167	likely_benign	0.0978	benign	-1.083	Destabilizing	None	N	0.112	neutral	N	0.493666121	None	None	N
T/V	0.1158	likely_benign	0.1135	benign	-0.27	Destabilizing	None	N	0.107	neutral	None	None	None	None	N
T/W	0.599	likely_pathogenic	0.5154	ambiguous	-0.638	Destabilizing	0.864	D	0.429	neutral	None	None	None	None	N
T/Y	0.2472	likely_benign	0.2112	benign	-0.419	Destabilizing	0.356	N	0.408	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.