TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18261	55006;55007;55008	chr2:178603906;178603905;178603904	chr2:179468633;179468632;179468631
N2AB	16620	50083;50084;50085	chr2:178603906;178603905;178603904	chr2:179468633;179468632;179468631
N2A	15693	47302;47303;47304	chr2:178603906;178603905;178603904	chr2:179468633;179468632;179468631
N2B	9196	27811;27812;27813	chr2:178603906;178603905;178603904	chr2:179468633;179468632;179468631
Novex-1	9321	28186;28187;28188	chr2:178603906;178603905;178603904	chr2:179468633;179468632;179468631
Novex-2	9388	28387;28388;28389	chr2:178603906;178603905;178603904	chr2:179468633;179468632;179468631
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: Fn3-20
• Domain position: 96
• Structural Position: 124
• Q(SASA): 0.2275
• 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	0.999	N	0.764	0.295	0.395289904662	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.446	ambiguous	0.3495	ambiguous	-0.671	Destabilizing	0.944	D	0.553	neutral	N	0.503913083	None	None	N
S/C	0.3783	ambiguous	0.373	ambiguous	-0.541	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
S/D	0.9753	likely_pathogenic	0.9712	pathogenic	-1.177	Destabilizing	0.991	D	0.629	neutral	None	None	None	None	N
S/E	0.9923	likely_pathogenic	0.9915	pathogenic	-1.047	Destabilizing	0.991	D	0.651	prob.neutral	None	None	None	None	N
S/F	0.9839	likely_pathogenic	0.973	pathogenic	-0.406	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
S/G	0.4108	ambiguous	0.3265	benign	-1.036	Destabilizing	0.991	D	0.625	neutral	None	None	None	None	N
S/H	0.9828	likely_pathogenic	0.9782	pathogenic	-1.462	Destabilizing	1.0	D	0.729	deleterious	None	None	None	None	N
S/I	0.9558	likely_pathogenic	0.9324	pathogenic	0.233	Stabilizing	0.995	D	0.822	deleterious	None	None	None	None	N
S/K	0.9986	likely_pathogenic	0.9982	pathogenic	-0.687	Destabilizing	0.991	D	0.629	neutral	None	None	None	None	N
S/L	0.8143	likely_pathogenic	0.7382	pathogenic	0.233	Stabilizing	0.976	D	0.82	deleterious	N	0.50427825	None	None	N
S/M	0.8727	likely_pathogenic	0.83	pathogenic	0.213	Stabilizing	1.0	D	0.729	deleterious	None	None	None	None	N
S/N	0.9154	likely_pathogenic	0.9051	pathogenic	-1.087	Destabilizing	0.991	D	0.647	neutral	None	None	None	None	N
S/P	0.9918	likely_pathogenic	0.9877	pathogenic	-0.032	Destabilizing	0.999	D	0.764	deleterious	N	0.521816755	None	None	N
S/Q	0.9891	likely_pathogenic	0.9868	pathogenic	-0.947	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
S/R	0.9972	likely_pathogenic	0.996	pathogenic	-0.89	Destabilizing	0.997	D	0.755	deleterious	None	None	None	None	N
S/T	0.1789	likely_benign	0.1379	benign	-0.822	Destabilizing	0.355	N	0.315	neutral	N	0.497274023	None	None	N
S/V	0.8937	likely_pathogenic	0.8337	pathogenic	-0.032	Destabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
S/W	0.9863	likely_pathogenic	0.9796	pathogenic	-0.634	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
S/Y	0.9818	likely_pathogenic	0.9746	pathogenic	-0.253	Destabilizing	0.999	D	0.817	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.