TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18309	55150;55151;55152	chr2:178602477;178602476;178602475	chr2:179467204;179467203;179467202
N2AB	16668	50227;50228;50229	chr2:178602477;178602476;178602475	chr2:179467204;179467203;179467202
N2A	15741	47446;47447;47448	chr2:178602477;178602476;178602475	chr2:179467204;179467203;179467202
N2B	9244	27955;27956;27957	chr2:178602477;178602476;178602475	chr2:179467204;179467203;179467202
Novex-1	9369	28330;28331;28332	chr2:178602477;178602476;178602475	chr2:179467204;179467203;179467202
Novex-2	9436	28531;28532;28533	chr2:178602477;178602476;178602475	chr2:179467204;179467203;179467202
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-21
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1165
• 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/L	rs1474621978	-0.414	0.247	N	0.511	0.18	0.491317756052	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
V/L	rs1474621978	-0.414	0.247	N	0.511	0.18	0.491317756052	gnomAD-4.0.0	6.84905E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00051E-07	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	0.7035	likely_pathogenic	0.6842	pathogenic	-2.5	Highly Destabilizing	0.822	D	0.609	neutral	D	0.548389794	None	None	N
V/C	0.9316	likely_pathogenic	0.9419	pathogenic	-2.014	Highly Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
V/D	0.997	likely_pathogenic	0.9976	pathogenic	-3.675	Highly Destabilizing	0.993	D	0.891	deleterious	None	None	None	None	N
V/E	0.9887	likely_pathogenic	0.9905	pathogenic	-3.368	Highly Destabilizing	0.99	D	0.891	deleterious	D	0.549150262	None	None	N
V/F	0.7647	likely_pathogenic	0.7842	pathogenic	-1.535	Destabilizing	0.956	D	0.822	deleterious	None	None	None	None	N
V/G	0.9203	likely_pathogenic	0.9335	pathogenic	-3.092	Highly Destabilizing	0.971	D	0.889	deleterious	D	0.549150262	None	None	N
V/H	0.9961	likely_pathogenic	0.9967	pathogenic	-2.977	Highly Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
V/I	0.0893	likely_benign	0.0854	benign	-0.776	Destabilizing	0.014	N	0.255	neutral	N	0.450760661	None	None	N
V/K	0.9897	likely_pathogenic	0.9907	pathogenic	-2.317	Highly Destabilizing	0.978	D	0.892	deleterious	None	None	None	None	N
V/L	0.3568	ambiguous	0.3725	ambiguous	-0.776	Destabilizing	0.247	N	0.511	neutral	N	0.488860476	None	None	N
V/M	0.5228	ambiguous	0.5378	ambiguous	-0.899	Destabilizing	0.956	D	0.693	prob.neutral	None	None	None	None	N
V/N	0.9909	likely_pathogenic	0.9931	pathogenic	-2.975	Highly Destabilizing	0.993	D	0.893	deleterious	None	None	None	None	N
V/P	0.9761	likely_pathogenic	0.9787	pathogenic	-1.333	Destabilizing	0.993	D	0.891	deleterious	None	None	None	None	N
V/Q	0.9849	likely_pathogenic	0.9864	pathogenic	-2.665	Highly Destabilizing	0.993	D	0.897	deleterious	None	None	None	None	N
V/R	0.9799	likely_pathogenic	0.9821	pathogenic	-2.274	Highly Destabilizing	0.993	D	0.893	deleterious	None	None	None	None	N
V/S	0.9483	likely_pathogenic	0.9516	pathogenic	-3.479	Highly Destabilizing	0.978	D	0.889	deleterious	None	None	None	None	N
V/T	0.7728	likely_pathogenic	0.7442	pathogenic	-3.019	Highly Destabilizing	0.86	D	0.667	neutral	None	None	None	None	N
V/W	0.9926	likely_pathogenic	0.9925	pathogenic	-2.161	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/Y	0.9813	likely_pathogenic	0.9829	pathogenic	-1.811	Destabilizing	0.978	D	0.821	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.