TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22273	67042;67043;67044	chr2:178580562;178580561;178580560	chr2:179445289;179445288;179445287
N2AB	20632	62119;62120;62121	chr2:178580562;178580561;178580560	chr2:179445289;179445288;179445287
N2A	19705	59338;59339;59340	chr2:178580562;178580561;178580560	chr2:179445289;179445288;179445287
N2B	13208	39847;39848;39849	chr2:178580562;178580561;178580560	chr2:179445289;179445288;179445287
Novex-1	13333	40222;40223;40224	chr2:178580562;178580561;178580560	chr2:179445289;179445288;179445287
Novex-2	13400	40423;40424;40425	chr2:178580562;178580561;178580560	chr2:179445289;179445288;179445287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-126
• Domain position: 9
• Structural Position: 16
• Q(SASA): 0.2863
• 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
L/I	None	None	0.698	N	0.463	0.073	0.514072065251	gnomAD-4.0.0	1.5946E-06	None	None	None	None	I	None	5.67344E-05	0	None	0	0	None	0	0	0	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
L/A	0.8617	likely_pathogenic	0.8405	pathogenic	-1.981	Destabilizing	0.754	D	0.473	neutral	None	None	None	None	I
L/C	0.8372	likely_pathogenic	0.8171	pathogenic	-1.192	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	I
L/D	0.996	likely_pathogenic	0.9944	pathogenic	-1.678	Destabilizing	0.993	D	0.673	neutral	None	None	None	None	I
L/E	0.9676	likely_pathogenic	0.9594	pathogenic	-1.527	Destabilizing	0.978	D	0.673	neutral	None	None	None	None	I
L/F	0.7035	likely_pathogenic	0.6353	pathogenic	-1.091	Destabilizing	0.032	N	0.377	neutral	N	0.502622177	None	None	I
L/G	0.975	likely_pathogenic	0.9719	pathogenic	-2.445	Highly Destabilizing	0.978	D	0.683	prob.neutral	None	None	None	None	I
L/H	0.9346	likely_pathogenic	0.9149	pathogenic	-1.673	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	I
L/I	0.1912	likely_benign	0.1624	benign	-0.696	Destabilizing	0.698	D	0.463	neutral	N	0.468333275	None	None	I
L/K	0.9322	likely_pathogenic	0.9209	pathogenic	-1.537	Destabilizing	0.978	D	0.625	neutral	None	None	None	None	I
L/M	0.343	ambiguous	0.304	benign	-0.559	Destabilizing	0.978	D	0.575	neutral	None	None	None	None	I
L/N	0.9705	likely_pathogenic	0.9613	pathogenic	-1.671	Destabilizing	0.993	D	0.668	neutral	None	None	None	None	I
L/P	0.9914	likely_pathogenic	0.9878	pathogenic	-1.099	Destabilizing	0.993	D	0.671	neutral	None	None	None	None	I
L/Q	0.8605	likely_pathogenic	0.8345	pathogenic	-1.629	Destabilizing	0.993	D	0.621	neutral	None	None	None	None	I
L/R	0.8982	likely_pathogenic	0.8795	pathogenic	-1.129	Destabilizing	0.978	D	0.621	neutral	None	None	None	None	I
L/S	0.9531	likely_pathogenic	0.9407	pathogenic	-2.369	Highly Destabilizing	0.971	D	0.625	neutral	N	0.502622177	None	None	I
L/T	0.8586	likely_pathogenic	0.8313	pathogenic	-2.084	Highly Destabilizing	0.956	D	0.583	neutral	None	None	None	None	I
L/V	0.2284	likely_benign	0.1963	benign	-1.099	Destabilizing	0.014	N	0.351	neutral	N	0.385346532	None	None	I
L/W	0.9394	likely_pathogenic	0.9149	pathogenic	-1.365	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	I
L/Y	0.9319	likely_pathogenic	0.9072	pathogenic	-1.068	Destabilizing	0.915	D	0.593	neutral	None	None	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.