TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17769	53530;53531;53532	chr2:178607297;178607296;178607295	chr2:179472024;179472023;179472022
N2AB	16128	48607;48608;48609	chr2:178607297;178607296;178607295	chr2:179472024;179472023;179472022
N2A	15201	45826;45827;45828	chr2:178607297;178607296;178607295	chr2:179472024;179472023;179472022
N2B	8704	26335;26336;26337	chr2:178607297;178607296;178607295	chr2:179472024;179472023;179472022
Novex-1	8829	26710;26711;26712	chr2:178607297;178607296;178607295	chr2:179472024;179472023;179472022
Novex-2	8896	26911;26912;26913	chr2:178607297;178607296;178607295	chr2:179472024;179472023;179472022
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: Fn3-17
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2402
• 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/V	rs759317677	-1.504	0.001	N	0.224	0.052	0.17948927462	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.63773E-04	None	0	0	0
L/V	rs759317677	-1.504	0.001	N	0.224	0.052	0.17948927462	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07297E-04	0
L/V	rs759317677	-1.504	0.001	N	0.224	0.052	0.17948927462	gnomAD-4.0.0	1.30233E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.08819E-04	3.20636E-05

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	0.2112	likely_benign	0.2077	benign	-1.249	Destabilizing	0.116	N	0.393	neutral	None	None	None	None	N
L/C	0.4428	ambiguous	0.4439	ambiguous	-0.732	Destabilizing	0.944	D	0.494	neutral	None	None	None	None	N
L/D	0.7814	likely_pathogenic	0.7771	pathogenic	-0.648	Destabilizing	0.69	D	0.565	neutral	None	None	None	None	N
L/E	0.3226	likely_benign	0.3093	benign	-0.688	Destabilizing	0.69	D	0.55	neutral	None	None	None	None	N
L/F	0.2719	likely_benign	0.2385	benign	-0.934	Destabilizing	0.627	D	0.488	neutral	N	0.468388337	None	None	N
L/G	0.4961	ambiguous	0.4931	ambiguous	-1.517	Destabilizing	0.69	D	0.52	neutral	None	None	None	None	N
L/H	0.2979	likely_benign	0.2606	benign	-0.705	Destabilizing	0.975	D	0.601	neutral	N	0.495132221	None	None	N
L/I	0.0977	likely_benign	0.0947	benign	-0.617	Destabilizing	0.033	N	0.443	neutral	N	0.493918713	None	None	N
L/K	0.1484	likely_benign	0.1443	benign	-0.816	Destabilizing	0.69	D	0.508	neutral	None	None	None	None	N
L/M	0.1148	likely_benign	0.1158	benign	-0.481	Destabilizing	0.69	D	0.51	neutral	None	None	None	None	N
L/N	0.3965	ambiguous	0.4003	ambiguous	-0.571	Destabilizing	0.69	D	0.57	neutral	None	None	None	None	N
L/P	0.8765	likely_pathogenic	0.8652	pathogenic	-0.795	Destabilizing	0.773	D	0.569	neutral	N	0.494612146	None	None	N
L/Q	0.1209	likely_benign	0.107	benign	-0.778	Destabilizing	0.818	D	0.542	neutral	None	None	None	None	N
L/R	0.1409	likely_benign	0.1259	benign	-0.195	Destabilizing	0.627	D	0.547	neutral	N	0.446050195	None	None	N
L/S	0.2795	likely_benign	0.2501	benign	-1.123	Destabilizing	0.241	N	0.409	neutral	None	None	None	None	N
L/T	0.1361	likely_benign	0.1354	benign	-1.047	Destabilizing	0.004	N	0.278	neutral	None	None	None	None	N
L/V	0.086	likely_benign	0.0829	benign	-0.795	Destabilizing	0.001	N	0.224	neutral	N	0.428579155	None	None	N
L/W	0.4846	ambiguous	0.4311	ambiguous	-0.965	Destabilizing	0.981	D	0.607	neutral	None	None	None	None	N
L/Y	0.5044	ambiguous	0.4863	ambiguous	-0.749	Destabilizing	0.818	D	0.489	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.