TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18096	54511;54512;54513	chr2:178604803;178604802;178604801	chr2:179469530;179469529;179469528
N2AB	16455	49588;49589;49590	chr2:178604803;178604802;178604801	chr2:179469530;179469529;179469528
N2A	15528	46807;46808;46809	chr2:178604803;178604802;178604801	chr2:179469530;179469529;179469528
N2B	9031	27316;27317;27318	chr2:178604803;178604802;178604801	chr2:179469530;179469529;179469528
Novex-1	9156	27691;27692;27693	chr2:178604803;178604802;178604801	chr2:179469530;179469529;179469528
Novex-2	9223	27892;27893;27894	chr2:178604803;178604802;178604801	chr2:179469530;179469529;179469528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-19
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.4313
• Predicted PPI site: I

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
E/K	None	None	0.998	N	0.543	0.362	0.365120060079	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/V	None	None	1.0	N	0.673	0.527	0.596093875869	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
E/A	0.2829	likely_benign	0.2616	benign	-0.216	Destabilizing	0.998	D	0.589	neutral	N	0.479405913	None	None	I
E/C	0.9325	likely_pathogenic	0.9334	pathogenic	0.019	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
E/D	0.1102	likely_benign	0.103	benign	-0.213	Destabilizing	0.434	N	0.218	neutral	N	0.468650201	None	None	I
E/F	0.906	likely_pathogenic	0.9073	pathogenic	-0.135	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
E/G	0.3902	ambiguous	0.3609	ambiguous	-0.388	Destabilizing	0.999	D	0.596	neutral	D	0.525255632	None	None	I
E/H	0.7441	likely_pathogenic	0.7208	pathogenic	0.202	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	I
E/I	0.594	likely_pathogenic	0.5734	pathogenic	0.191	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
E/K	0.4287	ambiguous	0.3657	ambiguous	0.489	Stabilizing	0.998	D	0.543	neutral	N	0.480501991	None	None	I
E/L	0.6446	likely_pathogenic	0.6233	pathogenic	0.191	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	I
E/M	0.6961	likely_pathogenic	0.6848	pathogenic	0.2	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	I
E/N	0.3546	ambiguous	0.3311	benign	0.167	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	I
E/P	0.5216	ambiguous	0.4873	ambiguous	0.075	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	I
E/Q	0.3134	likely_benign	0.2849	benign	0.205	Stabilizing	0.999	D	0.603	neutral	N	0.510016821	None	None	I
E/R	0.601	likely_pathogenic	0.5492	ambiguous	0.668	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
E/S	0.3418	ambiguous	0.3213	benign	0.021	Stabilizing	0.997	D	0.567	neutral	None	None	None	None	I
E/T	0.4094	ambiguous	0.3867	ambiguous	0.168	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	I
E/V	0.3926	ambiguous	0.374	ambiguous	0.075	Stabilizing	1.0	D	0.673	neutral	N	0.521233892	None	None	I
E/W	0.972	likely_pathogenic	0.9695	pathogenic	-0.015	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
E/Y	0.8298	likely_pathogenic	0.8253	pathogenic	0.107	Stabilizing	1.0	D	0.658	neutral	None	None	None	None	I

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.