TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29242	87949;87950;87951	chr2:178557538;178557537;178557536	chr2:179422265;179422264;179422263
N2AB	27601	83026;83027;83028	chr2:178557538;178557537;178557536	chr2:179422265;179422264;179422263
N2A	26674	80245;80246;80247	chr2:178557538;178557537;178557536	chr2:179422265;179422264;179422263
N2B	20177	60754;60755;60756	chr2:178557538;178557537;178557536	chr2:179422265;179422264;179422263
Novex-1	20302	61129;61130;61131	chr2:178557538;178557537;178557536	chr2:179422265;179422264;179422263
Novex-2	20369	61330;61331;61332	chr2:178557538;178557537;178557536	chr2:179422265;179422264;179422263
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: Fn3-101
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.3622
• 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/T	rs1416855828	None	0.999	N	0.557	0.216	0.225902525712	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/T	rs1416855828	None	0.999	N	0.557	0.216	0.225902525712	gnomAD-4.0.0	2.02983E-06	None	None	None	None	N	None	1.74679E-05	0	None	0	0	None	0	0	1.20492E-06	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	0.1396	likely_benign	0.1554	benign	-0.486	Destabilizing	0.997	D	0.465	neutral	N	0.499183752	None	None	N
S/C	0.2834	likely_benign	0.3648	ambiguous	-0.374	Destabilizing	1.0	D	0.823	deleterious	N	0.488640573	None	None	N
S/D	0.8851	likely_pathogenic	0.9106	pathogenic	-1.284	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
S/E	0.9396	likely_pathogenic	0.9473	pathogenic	-1.169	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
S/F	0.8123	likely_pathogenic	0.8648	pathogenic	-0.336	Destabilizing	1.0	D	0.895	deleterious	N	0.498982921	None	None	N
S/G	0.105	likely_benign	0.1227	benign	-0.841	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
S/H	0.8771	likely_pathogenic	0.9015	pathogenic	-1.517	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
S/I	0.8129	likely_pathogenic	0.8647	pathogenic	0.384	Stabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
S/K	0.9806	likely_pathogenic	0.9836	pathogenic	-0.715	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
S/L	0.4381	ambiguous	0.5369	ambiguous	0.384	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/M	0.6433	likely_pathogenic	0.694	pathogenic	0.433	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/N	0.594	likely_pathogenic	0.656	pathogenic	-1.095	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
S/P	0.7458	likely_pathogenic	0.8199	pathogenic	0.131	Stabilizing	1.0	D	0.858	deleterious	D	0.525196917	None	None	N
S/Q	0.9011	likely_pathogenic	0.9118	pathogenic	-0.939	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
S/R	0.9629	likely_pathogenic	0.9728	pathogenic	-1.001	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
S/T	0.2913	likely_benign	0.3243	benign	-0.754	Destabilizing	0.999	D	0.557	neutral	N	0.466647259	None	None	N
S/V	0.701	likely_pathogenic	0.7742	pathogenic	0.131	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
S/W	0.8883	likely_pathogenic	0.9268	pathogenic	-0.649	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
S/Y	0.7657	likely_pathogenic	0.8209	pathogenic	-0.243	Destabilizing	1.0	D	0.898	deleterious	N	0.497703672	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.