TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21534	64825;64826;64827	chr2:178585144;178585143;178585142	chr2:179449871;179449870;179449869
N2AB	19893	59902;59903;59904	chr2:178585144;178585143;178585142	chr2:179449871;179449870;179449869
N2A	18966	57121;57122;57123	chr2:178585144;178585143;178585142	chr2:179449871;179449870;179449869
N2B	12469	37630;37631;37632	chr2:178585144;178585143;178585142	chr2:179449871;179449870;179449869
Novex-1	12594	38005;38006;38007	chr2:178585144;178585143;178585142	chr2:179449871;179449870;179449869
Novex-2	12661	38206;38207;38208	chr2:178585144;178585143;178585142	chr2:179449871;179449870;179449869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-124
• Domain position: 66
• Structural Position: 151
• Q(SASA): 0.2183
• 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/G	rs768431801	-1.263	0.939	N	0.437	0.272	0.341226946553	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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	0.1085	likely_benign	0.1008	benign	-0.713	Destabilizing	0.807	D	0.375	neutral	None	None	None	None	N
S/C	0.1735	likely_benign	0.149	benign	-0.427	Destabilizing	0.999	D	0.731	prob.delet.	D	0.527958588	None	None	N
S/D	0.8868	likely_pathogenic	0.8269	pathogenic	0.258	Stabilizing	0.953	D	0.483	neutral	None	None	None	None	N
S/E	0.8959	likely_pathogenic	0.8504	pathogenic	0.234	Stabilizing	0.953	D	0.481	neutral	None	None	None	None	N
S/F	0.6911	likely_pathogenic	0.6255	pathogenic	-1.011	Destabilizing	0.993	D	0.821	deleterious	None	None	None	None	N
S/G	0.1235	likely_benign	0.1054	benign	-0.928	Destabilizing	0.939	D	0.437	neutral	N	0.487190948	None	None	N
S/H	0.8028	likely_pathogenic	0.7296	pathogenic	-1.385	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
S/I	0.5581	ambiguous	0.5179	ambiguous	-0.253	Destabilizing	0.982	D	0.798	deleterious	N	0.506878592	None	None	N
S/K	0.9559	likely_pathogenic	0.922	pathogenic	-0.508	Destabilizing	0.953	D	0.479	neutral	None	None	None	None	N
S/L	0.3317	likely_benign	0.2681	benign	-0.253	Destabilizing	0.91	D	0.618	neutral	None	None	None	None	N
S/M	0.4338	ambiguous	0.3783	ambiguous	-0.009	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
S/N	0.4759	ambiguous	0.3965	ambiguous	-0.401	Destabilizing	0.939	D	0.485	neutral	N	0.496977091	None	None	N
S/P	0.9682	likely_pathogenic	0.9599	pathogenic	-0.374	Destabilizing	0.993	D	0.753	deleterious	None	None	None	None	N
S/Q	0.8367	likely_pathogenic	0.7784	pathogenic	-0.554	Destabilizing	0.993	D	0.648	neutral	None	None	None	None	N
S/R	0.9084	likely_pathogenic	0.8594	pathogenic	-0.43	Destabilizing	0.991	D	0.765	deleterious	N	0.49335624	None	None	N
S/T	0.1263	likely_benign	0.1101	benign	-0.501	Destabilizing	0.17	N	0.361	neutral	N	0.509337322	None	None	N
S/V	0.4965	ambiguous	0.4534	ambiguous	-0.374	Destabilizing	0.973	D	0.703	prob.neutral	None	None	None	None	N
S/W	0.8577	likely_pathogenic	0.8062	pathogenic	-0.957	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
S/Y	0.6655	likely_pathogenic	0.5814	pathogenic	-0.693	Destabilizing	0.998	D	0.812	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.