TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16539	49840;49841;49842	chr2:178613194;178613193;178613192	chr2:179477921;179477920;179477919
N2AB	14898	44917;44918;44919	chr2:178613194;178613193;178613192	chr2:179477921;179477920;179477919
N2A	13971	42136;42137;42138	chr2:178613194;178613193;178613192	chr2:179477921;179477920;179477919
N2B	7474	22645;22646;22647	chr2:178613194;178613193;178613192	chr2:179477921;179477920;179477919
Novex-1	7599	23020;23021;23022	chr2:178613194;178613193;178613192	chr2:179477921;179477920;179477919
Novex-2	7666	23221;23222;23223	chr2:178613194;178613193;178613192	chr2:179477921;179477920;179477919
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-7
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.2476
• 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
S/L	rs1037901670	None	0.049	N	0.363	0.095	0.296679040009	gnomAD-4.0.0	3.19513E-06	None	None	None	None	N	None	5.69671E-05	0	None	0	0	None	0	0	0	0	3.03711E-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
S/A	0.0787	likely_benign	0.0651	benign	-0.777	Destabilizing	None	N	0.187	neutral	N	0.377949079	None	None	N
S/C	0.1484	likely_benign	0.1178	benign	-0.427	Destabilizing	0.703	D	0.44	neutral	None	None	None	None	N
S/D	0.4725	ambiguous	0.3305	benign	0.005	Stabilizing	0.064	N	0.279	neutral	None	None	None	None	N
S/E	0.483	ambiguous	0.3339	benign	0.002	Stabilizing	None	N	0.191	neutral	None	None	None	None	N
S/F	0.4	ambiguous	0.3173	benign	-0.906	Destabilizing	0.538	D	0.665	prob.neutral	None	None	None	None	N
S/G	0.1486	likely_benign	0.1209	benign	-1.028	Destabilizing	0.064	N	0.345	neutral	None	None	None	None	N
S/H	0.5457	ambiguous	0.4008	ambiguous	-1.462	Destabilizing	0.703	D	0.435	neutral	None	None	None	None	N
S/I	0.2241	likely_benign	0.1609	benign	-0.214	Destabilizing	0.001	N	0.395	neutral	None	None	None	None	N
S/K	0.881	likely_pathogenic	0.7722	pathogenic	-0.667	Destabilizing	0.064	N	0.285	neutral	None	None	None	None	N
S/L	0.1939	likely_benign	0.1566	benign	-0.214	Destabilizing	0.049	N	0.363	neutral	N	0.450266745	None	None	N
S/M	0.2444	likely_benign	0.1744	benign	0.009	Stabilizing	0.538	D	0.431	neutral	None	None	None	None	N
S/N	0.1691	likely_benign	0.1272	benign	-0.55	Destabilizing	0.25	N	0.361	neutral	None	None	None	None	N
S/P	0.1612	likely_benign	0.1035	benign	-0.368	Destabilizing	None	N	0.279	neutral	N	0.361136727	None	None	N
S/Q	0.6012	likely_pathogenic	0.4231	ambiguous	-0.676	Destabilizing	0.143	N	0.399	neutral	None	None	None	None	N
S/R	0.8717	likely_pathogenic	0.7845	pathogenic	-0.595	Destabilizing	0.25	N	0.544	neutral	None	None	None	None	N
S/T	0.1072	likely_benign	0.0886	benign	-0.603	Destabilizing	0.094	N	0.284	neutral	N	0.449817458	None	None	N
S/V	0.2137	likely_benign	0.1469	benign	-0.368	Destabilizing	0.064	N	0.365	neutral	None	None	None	None	N
S/W	0.5497	ambiguous	0.489	ambiguous	-0.869	Destabilizing	0.964	D	0.693	prob.delet.	None	None	None	None	N
S/Y	0.3227	likely_benign	0.2733	benign	-0.62	Destabilizing	0.878	D	0.629	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.