TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14559	43900;43901;43902	chr2:178632219;178632218;178632217	chr2:179496946;179496945;179496944
N2AB	12918	38977;38978;38979	chr2:178632219;178632218;178632217	chr2:179496946;179496945;179496944
N2A	11991	36196;36197;36198	chr2:178632219;178632218;178632217	chr2:179496946;179496945;179496944
N2B	5494	16705;16706;16707	chr2:178632219;178632218;178632217	chr2:179496946;179496945;179496944
Novex-1	5619	17080;17081;17082	chr2:178632219;178632218;178632217	chr2:179496946;179496945;179496944
Novex-2	5686	17281;17282;17283	chr2:178632219;178632218;178632217	chr2:179496946;179496945;179496944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-96
• Domain position: 63
• Structural Position: 145
• Q(SASA): 0.1781
• 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/P	None	None	0.773	D	0.309	0.323	0.336647302497	gnomAD-4.0.0	1.60607E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45645E-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
S/A	0.1084	likely_benign	0.092	benign	-0.592	Destabilizing	0.003	N	0.146	neutral	N	0.508607416	None	None	N
S/C	0.1325	likely_benign	0.1287	benign	-0.452	Destabilizing	0.928	D	0.347	neutral	D	0.562697157	None	None	N
S/D	0.3572	ambiguous	0.2899	benign	-0.126	Destabilizing	0.241	N	0.311	neutral	None	None	None	None	N
S/E	0.5457	ambiguous	0.4682	ambiguous	-0.183	Destabilizing	0.388	N	0.313	neutral	None	None	None	None	N
S/F	0.2838	likely_benign	0.2221	benign	-0.956	Destabilizing	0.773	D	0.406	neutral	D	0.560940898	None	None	N
S/G	0.1075	likely_benign	0.0934	benign	-0.772	Destabilizing	0.116	N	0.342	neutral	None	None	None	None	N
S/H	0.3262	likely_benign	0.2885	benign	-1.266	Destabilizing	0.818	D	0.349	neutral	None	None	None	None	N
S/I	0.2945	likely_benign	0.2418	benign	-0.237	Destabilizing	0.527	D	0.36	neutral	None	None	None	None	N
S/K	0.56	ambiguous	0.4796	ambiguous	-0.695	Destabilizing	0.388	N	0.309	neutral	None	None	None	None	N
S/L	0.1274	likely_benign	0.1078	benign	-0.237	Destabilizing	0.241	N	0.36	neutral	None	None	None	None	N
S/M	0.2682	likely_benign	0.2307	benign	0.086	Stabilizing	0.818	D	0.347	neutral	None	None	None	None	N
S/N	0.1376	likely_benign	0.1113	benign	-0.518	Destabilizing	0.002	N	0.228	neutral	None	None	None	None	N
S/P	0.644	likely_pathogenic	0.5985	pathogenic	-0.324	Destabilizing	0.773	D	0.309	neutral	D	0.561869691	None	None	N
S/Q	0.5073	ambiguous	0.442	ambiguous	-0.774	Destabilizing	0.818	D	0.354	neutral	None	None	None	None	N
S/R	0.4434	ambiguous	0.3751	ambiguous	-0.475	Destabilizing	0.69	D	0.316	neutral	None	None	None	None	N
S/T	0.0837	likely_benign	0.0791	benign	-0.604	Destabilizing	None	N	0.121	neutral	N	0.421487105	None	None	N
S/V	0.2967	likely_benign	0.2408	benign	-0.324	Destabilizing	0.241	N	0.359	neutral	None	None	None	None	N
S/W	0.4323	ambiguous	0.3721	ambiguous	-0.906	Destabilizing	0.981	D	0.482	neutral	None	None	None	None	N
S/Y	0.2337	likely_benign	0.1953	benign	-0.658	Destabilizing	0.773	D	0.413	neutral	D	0.561869691	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.