TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31150	93673;93674;93675	chr2:178548178;178548177;178548176	chr2:179412905;179412904;179412903
N2AB	29509	88750;88751;88752	chr2:178548178;178548177;178548176	chr2:179412905;179412904;179412903
N2A	28582	85969;85970;85971	chr2:178548178;178548177;178548176	chr2:179412905;179412904;179412903
N2B	22085	66478;66479;66480	chr2:178548178;178548177;178548176	chr2:179412905;179412904;179412903
Novex-1	22210	66853;66854;66855	chr2:178548178;178548177;178548176	chr2:179412905;179412904;179412903
Novex-2	22277	67054;67055;67056	chr2:178548178;178548177;178548176	chr2:179412905;179412904;179412903
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-115
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0865
• 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
L/P	None	None	0.99	N	0.873	0.585	0.790458859785	gnomAD-4.0.0	1.59107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
L/A	0.7003	likely_pathogenic	0.6889	pathogenic	-3.115	Highly Destabilizing	0.717	D	0.653	neutral	None	None	None	None	N
L/C	0.7687	likely_pathogenic	0.7537	pathogenic	-2.071	Highly Destabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
L/D	0.9973	likely_pathogenic	0.9969	pathogenic	-3.68	Highly Destabilizing	0.993	D	0.874	deleterious	None	None	None	None	N
L/E	0.9827	likely_pathogenic	0.9787	pathogenic	-3.358	Highly Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
L/F	0.6432	likely_pathogenic	0.638	pathogenic	-1.861	Destabilizing	0.942	D	0.664	neutral	N	0.478199775	None	None	N
L/G	0.959	likely_pathogenic	0.9542	pathogenic	-3.697	Highly Destabilizing	0.978	D	0.853	deleterious	None	None	None	None	N
L/H	0.9712	likely_pathogenic	0.9659	pathogenic	-3.256	Highly Destabilizing	0.997	D	0.875	deleterious	N	0.489974154	None	None	N
L/I	0.0792	likely_benign	0.0828	benign	-1.334	Destabilizing	0.014	N	0.31	neutral	N	0.367306984	None	None	N
L/K	0.9827	likely_pathogenic	0.9781	pathogenic	-2.421	Highly Destabilizing	0.978	D	0.815	deleterious	None	None	None	None	N
L/M	0.2596	likely_benign	0.2627	benign	-1.473	Destabilizing	0.956	D	0.617	neutral	None	None	None	None	N
L/N	0.9833	likely_pathogenic	0.9823	pathogenic	-3.168	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
L/P	0.9516	likely_pathogenic	0.9432	pathogenic	-1.924	Destabilizing	0.99	D	0.873	deleterious	N	0.478453265	None	None	N
L/Q	0.9535	likely_pathogenic	0.945	pathogenic	-2.804	Highly Destabilizing	0.993	D	0.868	deleterious	None	None	None	None	N
L/R	0.9637	likely_pathogenic	0.9532	pathogenic	-2.454	Highly Destabilizing	0.99	D	0.857	deleterious	N	0.489974154	None	None	N
L/S	0.9467	likely_pathogenic	0.9468	pathogenic	-3.654	Highly Destabilizing	0.978	D	0.783	deleterious	None	None	None	None	N
L/T	0.6995	likely_pathogenic	0.7134	pathogenic	-3.177	Highly Destabilizing	0.86	D	0.651	neutral	None	None	None	None	N
L/V	0.071	likely_benign	0.0732	benign	-1.924	Destabilizing	0.025	N	0.322	neutral	N	0.345387343	None	None	N
L/W	0.9405	likely_pathogenic	0.9239	pathogenic	-2.154	Highly Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
L/Y	0.9597	likely_pathogenic	0.9542	pathogenic	-2.081	Highly Destabilizing	0.978	D	0.757	deleterious	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.