TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27102	81529;81530;81531	chr2:178564828;178564827;178564826	chr2:179429555;179429554;179429553
N2AB	25461	76606;76607;76608	chr2:178564828;178564827;178564826	chr2:179429555;179429554;179429553
N2A	24534	73825;73826;73827	chr2:178564828;178564827;178564826	chr2:179429555;179429554;179429553
N2B	18037	54334;54335;54336	chr2:178564828;178564827;178564826	chr2:179429555;179429554;179429553
Novex-1	18162	54709;54710;54711	chr2:178564828;178564827;178564826	chr2:179429555;179429554;179429553
Novex-2	18229	54910;54911;54912	chr2:178564828;178564827;178564826	chr2:179429555;179429554;179429553
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-85
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3346
• 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
T/I	rs760944577	None	0.003	N	0.469	0.122	0.273503213844	gnomAD-4.0.0	2.05358E-06	None	None	None	None	I	None	0	0	None	0	7.5861E-05	None	0	0	0	0	0
T/S	None	-1.005	None	N	0.279	0.176	0.110078149338	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
T/S	None	-1.005	None	N	0.279	0.176	0.110078149338	gnomAD-4.0.0	6.84526E-07	None	None	None	None	I	None	0	2.23914E-05	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
T/A	0.0907	likely_benign	0.0909	benign	-0.639	Destabilizing	None	N	0.283	neutral	N	0.39503509	None	None	I
T/C	0.2125	likely_benign	0.2342	benign	-0.334	Destabilizing	0.041	N	0.644	neutral	None	None	None	None	I
T/D	0.6365	likely_pathogenic	0.5791	pathogenic	0.059	Stabilizing	None	N	0.399	neutral	None	None	None	None	I
T/E	0.6613	likely_pathogenic	0.6191	pathogenic	0.026	Stabilizing	None	N	0.396	neutral	None	None	None	None	I
T/F	0.479	ambiguous	0.4866	ambiguous	-0.89	Destabilizing	0.018	N	0.564	neutral	None	None	None	None	I
T/G	0.1744	likely_benign	0.1914	benign	-0.851	Destabilizing	None	N	0.386	neutral	None	None	None	None	I
T/H	0.4638	ambiguous	0.4539	ambiguous	-1.165	Destabilizing	0.041	N	0.627	neutral	None	None	None	None	I
T/I	0.4679	ambiguous	0.4298	ambiguous	-0.183	Destabilizing	0.003	N	0.469	neutral	N	0.462414875	None	None	I
T/K	0.6561	likely_pathogenic	0.6193	pathogenic	-0.582	Destabilizing	None	N	0.4	neutral	None	None	None	None	I
T/L	0.1895	likely_benign	0.178	benign	-0.183	Destabilizing	0.002	N	0.425	neutral	None	None	None	None	I
T/M	0.1511	likely_benign	0.1294	benign	0.093	Stabilizing	0.116	N	0.624	neutral	None	None	None	None	I
T/N	0.1813	likely_benign	0.1599	benign	-0.427	Destabilizing	None	N	0.385	neutral	N	0.425069995	None	None	I
T/P	0.7815	likely_pathogenic	0.7646	pathogenic	-0.303	Destabilizing	0.001	N	0.472	neutral	N	0.487715965	None	None	I
T/Q	0.508	ambiguous	0.4758	ambiguous	-0.612	Destabilizing	0.002	N	0.471	neutral	None	None	None	None	I
T/R	0.572	likely_pathogenic	0.5428	ambiguous	-0.342	Destabilizing	0.004	N	0.473	neutral	None	None	None	None	I
T/S	0.0601	likely_benign	0.064	benign	-0.692	Destabilizing	None	N	0.279	neutral	N	0.284192529	None	None	I
T/V	0.3043	likely_benign	0.2779	benign	-0.303	Destabilizing	0.002	N	0.429	neutral	None	None	None	None	I
T/W	0.767	likely_pathogenic	0.7907	pathogenic	-0.846	Destabilizing	0.316	N	0.624	neutral	None	None	None	None	I
T/Y	0.4353	ambiguous	0.466	ambiguous	-0.6	Destabilizing	0.018	N	0.572	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.