TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16196	48811;48812;48813	chr2:178615359;178615358;178615357	chr2:179480086;179480085;179480084
N2AB	14555	43888;43889;43890	chr2:178615359;178615358;178615357	chr2:179480086;179480085;179480084
N2A	13628	41107;41108;41109	chr2:178615359;178615358;178615357	chr2:179480086;179480085;179480084
N2B	7131	21616;21617;21618	chr2:178615359;178615358;178615357	chr2:179480086;179480085;179480084
Novex-1	7256	21991;21992;21993	chr2:178615359;178615358;178615357	chr2:179480086;179480085;179480084
Novex-2	7323	22192;22193;22194	chr2:178615359;178615358;178615357	chr2:179480086;179480085;179480084
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-5
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3043
• 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
P/L	rs1485291993	None	0.001	N	0.292	0.266	0.441740949975	gnomAD-4.0.0	2.73891E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.6E-06	0	0
P/S	None	None	0.183	N	0.356	0.257	0.17258766438	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
P/A	0.0746	likely_benign	0.0696	benign	-1.428	Destabilizing	0.183	N	0.385	neutral	N	0.400816944	None	None	N
P/C	0.4626	ambiguous	0.4082	ambiguous	-1.049	Destabilizing	0.983	D	0.435	neutral	None	None	None	None	N
P/D	0.434	ambiguous	0.4227	ambiguous	-0.852	Destabilizing	0.418	N	0.369	neutral	None	None	None	None	N
P/E	0.179	likely_benign	0.1782	benign	-0.848	Destabilizing	0.129	N	0.401	neutral	None	None	None	None	N
P/F	0.4013	ambiguous	0.3654	ambiguous	-1.116	Destabilizing	0.557	D	0.449	neutral	None	None	None	None	N
P/G	0.3076	likely_benign	0.2797	benign	-1.751	Destabilizing	0.418	N	0.385	neutral	None	None	None	None	N
P/H	0.2295	likely_benign	0.1955	benign	-1.25	Destabilizing	0.836	D	0.429	neutral	None	None	None	None	N
P/I	0.1965	likely_benign	0.1826	benign	-0.647	Destabilizing	0.264	N	0.431	neutral	None	None	None	None	N
P/K	0.285	likely_benign	0.2576	benign	-1.043	Destabilizing	0.004	N	0.165	neutral	None	None	None	None	N
P/L	0.0918	likely_benign	0.0847	benign	-0.647	Destabilizing	0.001	N	0.292	neutral	N	0.459318289	None	None	N
P/M	0.2081	likely_benign	0.2003	benign	-0.558	Destabilizing	0.716	D	0.431	neutral	None	None	None	None	N
P/N	0.3319	likely_benign	0.3175	benign	-0.829	Destabilizing	0.418	N	0.387	neutral	None	None	None	None	N
P/Q	0.1156	likely_benign	0.1051	benign	-0.976	Destabilizing	0.001	N	0.167	neutral	N	0.346308768	None	None	N
P/R	0.216	likely_benign	0.1813	benign	-0.589	Destabilizing	0.213	N	0.383	neutral	N	0.424371621	None	None	N
P/S	0.1264	likely_benign	0.113	benign	-1.44	Destabilizing	0.183	N	0.356	neutral	N	0.436682424	None	None	N
P/T	0.1099	likely_benign	0.0983	benign	-1.314	Destabilizing	0.351	N	0.373	neutral	N	0.43246776	None	None	N
P/V	0.139	likely_benign	0.1342	benign	-0.871	Destabilizing	0.129	N	0.388	neutral	None	None	None	None	N
P/W	0.6363	likely_pathogenic	0.582	pathogenic	-1.261	Destabilizing	0.983	D	0.456	neutral	None	None	None	None	N
P/Y	0.4501	ambiguous	0.4148	ambiguous	-0.964	Destabilizing	0.836	D	0.454	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.