TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18196	54811;54812;54813	chr2:178604101;178604100;178604099	chr2:179468828;179468827;179468826
N2AB	16555	49888;49889;49890	chr2:178604101;178604100;178604099	chr2:179468828;179468827;179468826
N2A	15628	47107;47108;47109	chr2:178604101;178604100;178604099	chr2:179468828;179468827;179468826
N2B	9131	27616;27617;27618	chr2:178604101;178604100;178604099	chr2:179468828;179468827;179468826
Novex-1	9256	27991;27992;27993	chr2:178604101;178604100;178604099	chr2:179468828;179468827;179468826
Novex-2	9323	28192;28193;28194	chr2:178604101;178604100;178604099	chr2:179468828;179468827;179468826
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-20
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2397
• Predicted PPI site: I

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
S/P	None	None	0.983	D	0.661	0.458	0.319970858106	gnomAD-4.0.0	1.59371E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43451E-05	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
S/A	0.128	likely_benign	0.1041	benign	-0.448	Destabilizing	0.025	N	0.422	neutral	N	0.506283083	None	None	I
S/C	0.1262	likely_benign	0.1234	benign	-0.223	Destabilizing	0.995	D	0.644	neutral	N	0.482248245	None	None	I
S/D	0.9179	likely_pathogenic	0.9247	pathogenic	-0.348	Destabilizing	0.957	D	0.701	prob.neutral	None	None	None	None	I
S/E	0.9135	likely_pathogenic	0.9017	pathogenic	-0.426	Destabilizing	0.916	D	0.683	prob.neutral	None	None	None	None	I
S/F	0.5603	ambiguous	0.4553	ambiguous	-0.965	Destabilizing	0.983	D	0.709	prob.delet.	N	0.507265034	None	None	I
S/G	0.2965	likely_benign	0.2838	benign	-0.598	Destabilizing	0.845	D	0.597	neutral	None	None	None	None	I
S/H	0.6567	likely_pathogenic	0.6272	pathogenic	-1.207	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
S/I	0.6412	likely_pathogenic	0.5583	ambiguous	-0.174	Destabilizing	0.975	D	0.72	prob.delet.	None	None	None	None	I
S/K	0.9522	likely_pathogenic	0.9394	pathogenic	-0.616	Destabilizing	0.916	D	0.691	prob.neutral	None	None	None	None	I
S/L	0.248	likely_benign	0.2071	benign	-0.174	Destabilizing	0.845	D	0.68	prob.neutral	None	None	None	None	I
S/M	0.4242	ambiguous	0.3944	ambiguous	0.289	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	I
S/N	0.4512	ambiguous	0.4295	ambiguous	-0.381	Destabilizing	0.987	D	0.719	prob.delet.	None	None	None	None	I
S/P	0.9857	likely_pathogenic	0.9739	pathogenic	-0.235	Destabilizing	0.983	D	0.661	neutral	D	0.53350959	None	None	I
S/Q	0.7767	likely_pathogenic	0.7499	pathogenic	-0.69	Destabilizing	0.987	D	0.708	prob.delet.	None	None	None	None	I
S/R	0.9277	likely_pathogenic	0.9002	pathogenic	-0.373	Destabilizing	0.987	D	0.66	neutral	None	None	None	None	I
S/T	0.3131	likely_benign	0.2873	benign	-0.428	Destabilizing	0.892	D	0.619	neutral	N	0.474308527	None	None	I
S/V	0.5155	ambiguous	0.4202	ambiguous	-0.235	Destabilizing	0.95	D	0.693	prob.neutral	None	None	None	None	I
S/W	0.7615	likely_pathogenic	0.7239	pathogenic	-0.956	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
S/Y	0.4785	ambiguous	0.4226	ambiguous	-0.685	Destabilizing	0.994	D	0.709	prob.delet.	N	0.51556992	None	None	I

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.