TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33328	100207;100208;100209	chr2:178537127;178537126;178537125	chr2:179401854;179401853;179401852
N2AB	31687	95284;95285;95286	chr2:178537127;178537126;178537125	chr2:179401854;179401853;179401852
N2A	30760	92503;92504;92505	chr2:178537127;178537126;178537125	chr2:179401854;179401853;179401852
N2B	24263	73012;73013;73014	chr2:178537127;178537126;178537125	chr2:179401854;179401853;179401852
Novex-1	24388	73387;73388;73389	chr2:178537127;178537126;178537125	chr2:179401854;179401853;179401852
Novex-2	24455	73588;73589;73590	chr2:178537127;178537126;178537125	chr2:179401854;179401853;179401852
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-130
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0925
• 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
V/M	rs372302484	-0.781	0.942	D	0.665	0.374	None	gnomAD-2.1.1	3.94E-05	None	None	None	None	N	None	4.14147E-04	0	None	0	5.14E-05	None	0	None	0	0	0
V/M	rs372302484	-0.781	0.942	D	0.665	0.374	None	gnomAD-3.1.2	1.05139E-04	None	None	None	None	N	None	3.85951E-04	0	0	0	0	None	0	0	0	0	0
V/M	rs372302484	-0.781	0.942	D	0.665	0.374	None	gnomAD-4.0.0	2.23136E-05	None	None	None	None	N	None	4.80538E-04	0	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
V/A	0.8772	likely_pathogenic	0.8212	pathogenic	-2.255	Highly Destabilizing	0.698	D	0.551	neutral	D	0.53670432	None	None	N
V/C	0.9829	likely_pathogenic	0.9817	pathogenic	-1.776	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.9988	pathogenic	-2.964	Highly Destabilizing	0.956	D	0.884	deleterious	None	None	None	None	N
V/E	0.9961	likely_pathogenic	0.9947	pathogenic	-2.66	Highly Destabilizing	0.942	D	0.847	deleterious	D	0.555569043	None	None	N
V/F	0.915	likely_pathogenic	0.8856	pathogenic	-1.264	Destabilizing	0.956	D	0.748	deleterious	None	None	None	None	N
V/G	0.9697	likely_pathogenic	0.9647	pathogenic	-2.875	Highly Destabilizing	0.942	D	0.84	deleterious	D	0.555569043	None	None	N
V/H	0.9994	likely_pathogenic	0.999	pathogenic	-2.722	Highly Destabilizing	0.998	D	0.878	deleterious	None	None	None	None	N
V/I	0.1056	likely_benign	0.0993	benign	-0.476	Destabilizing	0.019	N	0.273	neutral	None	None	None	None	N
V/K	0.9973	likely_pathogenic	0.9963	pathogenic	-1.829	Destabilizing	0.956	D	0.845	deleterious	None	None	None	None	N
V/L	0.5688	likely_pathogenic	0.5988	pathogenic	-0.476	Destabilizing	0.489	N	0.559	neutral	D	0.530611098	None	None	N
V/M	0.762	likely_pathogenic	0.7258	pathogenic	-0.688	Destabilizing	0.942	D	0.665	neutral	D	0.525601504	None	None	N
V/N	0.9979	likely_pathogenic	0.9968	pathogenic	-2.405	Highly Destabilizing	0.978	D	0.902	deleterious	None	None	None	None	N
V/P	0.9975	likely_pathogenic	0.9964	pathogenic	-1.046	Destabilizing	0.043	N	0.689	prob.neutral	None	None	None	None	N
V/Q	0.9963	likely_pathogenic	0.9946	pathogenic	-2.079	Highly Destabilizing	0.978	D	0.89	deleterious	None	None	None	None	N
V/R	0.9941	likely_pathogenic	0.9918	pathogenic	-1.884	Destabilizing	0.978	D	0.9	deleterious	None	None	None	None	N
V/S	0.9868	likely_pathogenic	0.9776	pathogenic	-3.019	Highly Destabilizing	0.956	D	0.813	deleterious	None	None	None	None	N
V/T	0.9253	likely_pathogenic	0.877	pathogenic	-2.549	Highly Destabilizing	0.86	D	0.563	neutral	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.9986	pathogenic	-1.83	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
V/Y	0.9966	likely_pathogenic	0.9944	pathogenic	-1.459	Destabilizing	0.993	D	0.76	deleterious	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.