TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6247	18964;18965;18966	chr2:178729417;178729416;178729415	chr2:179594144;179594143;179594142
N2AB	5930	18013;18014;18015	chr2:178729417;178729416;178729415	chr2:179594144;179594143;179594142
N2A	5003	15232;15233;15234	chr2:178729417;178729416;178729415	chr2:179594144;179594143;179594142
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-46
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2844
• 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/W	rs2079986312	None	0.915	N	0.602	0.455	0.872719117219	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/W	rs2079986312	None	0.915	N	0.602	0.455	0.872719117219	gnomAD-4.0.0	2.56276E-06	None	None	None	None	N	None	1.69205E-05	0	None	0	2.42507E-05	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	0.1778	likely_benign	0.2155	benign	-1.741	Destabilizing	0.035	N	0.439	neutral	None	None	None	None	N
L/C	0.4312	ambiguous	0.4877	ambiguous	-1.282	Destabilizing	0.824	D	0.574	neutral	None	None	None	None	N
L/D	0.6623	likely_pathogenic	0.7059	pathogenic	-0.729	Destabilizing	0.555	D	0.638	neutral	None	None	None	None	N
L/E	0.3289	likely_benign	0.3486	ambiguous	-0.695	Destabilizing	0.555	D	0.639	neutral	None	None	None	None	N
L/F	0.0981	likely_benign	0.1121	benign	-1.258	Destabilizing	None	N	0.271	neutral	N	0.454233401	None	None	N
L/G	0.4101	ambiguous	0.4738	ambiguous	-2.095	Highly Destabilizing	0.149	N	0.628	neutral	None	None	None	None	N
L/H	0.1855	likely_benign	0.2053	benign	-1.276	Destabilizing	0.935	D	0.627	neutral	None	None	None	None	N
L/I	0.0772	likely_benign	0.0846	benign	-0.828	Destabilizing	0.001	N	0.147	neutral	None	None	None	None	N
L/K	0.2142	likely_benign	0.2392	benign	-1.04	Destabilizing	0.38	N	0.597	neutral	None	None	None	None	N
L/M	0.0771	likely_benign	0.0866	benign	-0.743	Destabilizing	0.002	N	0.172	neutral	N	0.474280599	None	None	N
L/N	0.3482	ambiguous	0.4126	ambiguous	-0.909	Destabilizing	0.555	D	0.637	neutral	None	None	None	None	N
L/P	0.3848	ambiguous	0.4054	ambiguous	-1.101	Destabilizing	0.791	D	0.638	neutral	None	None	None	None	N
L/Q	0.1329	likely_benign	0.1455	benign	-1.02	Destabilizing	0.38	N	0.613	neutral	None	None	None	None	N
L/R	0.1684	likely_benign	0.1737	benign	-0.55	Destabilizing	0.38	N	0.613	neutral	None	None	None	None	N
L/S	0.2032	likely_benign	0.2418	benign	-1.657	Destabilizing	0.117	N	0.553	neutral	D	0.530347313	None	None	N
L/T	0.1542	likely_benign	0.1899	benign	-1.485	Destabilizing	0.149	N	0.498	neutral	None	None	None	None	N
L/V	0.0734	likely_benign	0.0791	benign	-1.101	Destabilizing	None	N	0.112	neutral	N	0.468677205	None	None	N
L/W	0.2032	likely_benign	0.213	benign	-1.29	Destabilizing	0.915	D	0.602	neutral	N	0.502586178	None	None	N
L/Y	0.2571	likely_benign	0.3008	benign	-1.056	Destabilizing	0.235	N	0.576	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.