TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22602	68029;68030;68031	chr2:178579226;178579225;178579224	chr2:179443953;179443952;179443951
N2AB	20961	63106;63107;63108	chr2:178579226;178579225;178579224	chr2:179443953;179443952;179443951
N2A	20034	60325;60326;60327	chr2:178579226;178579225;178579224	chr2:179443953;179443952;179443951
N2B	13537	40834;40835;40836	chr2:178579226;178579225;178579224	chr2:179443953;179443952;179443951
Novex-1	13662	41209;41210;41211	chr2:178579226;178579225;178579224	chr2:179443953;179443952;179443951
Novex-2	13729	41410;41411;41412	chr2:178579226;178579225;178579224	chr2:179443953;179443952;179443951
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-127
• Domain position: 43
• Structural Position: 130
• Q(SASA): 0.3101
• 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/C	None	None	0.883	N	0.413	0.415	0.524480850804	gnomAD-4.0.0	8.40227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.25325E-04	0
S/F	None	None	0.667	N	0.467	0.436	0.674675629537	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
S/P	rs780276317	None	0.667	N	0.336	0.21	0.258283824007	gnomAD-4.0.0	1.59188E-06	None	None	None	None	N	None	5.66316E-05	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
S/A	0.1714	likely_benign	0.1474	benign	-0.403	Destabilizing	0.055	N	0.391	neutral	N	0.514145709	None	None	N
S/C	0.2142	likely_benign	0.2117	benign	-0.265	Destabilizing	0.883	D	0.413	neutral	N	0.49400135	None	None	N
S/D	0.4574	ambiguous	0.4021	ambiguous	0.161	Stabilizing	0.272	N	0.347	neutral	None	None	None	None	N
S/E	0.7783	likely_pathogenic	0.709	pathogenic	0.062	Stabilizing	0.272	N	0.345	neutral	None	None	None	None	N
S/F	0.5015	ambiguous	0.4191	ambiguous	-1.053	Destabilizing	0.667	D	0.467	neutral	N	0.49374786	None	None	N
S/G	0.123	likely_benign	0.1115	benign	-0.497	Destabilizing	0.272	N	0.37	neutral	None	None	None	None	N
S/H	0.5556	ambiguous	0.5508	ambiguous	-1.003	Destabilizing	0.968	D	0.408	neutral	None	None	None	None	N
S/I	0.5218	ambiguous	0.4299	ambiguous	-0.288	Destabilizing	0.396	N	0.418	neutral	None	None	None	None	N
S/K	0.8559	likely_pathogenic	0.8245	pathogenic	-0.406	Destabilizing	0.272	N	0.344	neutral	None	None	None	None	N
S/L	0.1745	likely_benign	0.1462	benign	-0.288	Destabilizing	0.157	N	0.4	neutral	None	None	None	None	N
S/M	0.2828	likely_benign	0.2708	benign	0.019	Stabilizing	0.909	D	0.403	neutral	None	None	None	None	N
S/N	0.1754	likely_benign	0.162	benign	-0.16	Destabilizing	0.272	N	0.387	neutral	None	None	None	None	N
S/P	0.7995	likely_pathogenic	0.748	pathogenic	-0.299	Destabilizing	0.667	D	0.336	neutral	N	0.488467941	None	None	N
S/Q	0.751	likely_pathogenic	0.7333	pathogenic	-0.428	Destabilizing	0.726	D	0.389	neutral	None	None	None	None	N
S/R	0.8282	likely_pathogenic	0.7999	pathogenic	-0.196	Destabilizing	0.567	D	0.336	neutral	None	None	None	None	N
S/T	0.0642	likely_benign	0.0647	benign	-0.282	Destabilizing	None	N	0.176	neutral	N	0.444419052	None	None	N
S/V	0.4143	ambiguous	0.3567	ambiguous	-0.299	Destabilizing	0.157	N	0.399	neutral	None	None	None	None	N
S/W	0.6406	likely_pathogenic	0.6036	pathogenic	-1.05	Destabilizing	0.968	D	0.581	neutral	None	None	None	None	N
S/Y	0.4373	ambiguous	0.39	ambiguous	-0.767	Destabilizing	0.667	D	0.478	neutral	D	0.529904596	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.