Hereditary neuropathy or pain disorder

STR: RFC1_AAGGG

Green List (high evidence)

Pathogenicity at the RFC1_AAGGG repeat locus can result from the biallelic replacement of the benign AAAAG repeat with a variable number of AAGGG repeats (PMID: 30926972; 32040566). Furthermore, biallelic expansions of (AAAAG)exp/(AAAGG)exp, (AAAAG)exp/(AAGGG)exp or (AAAGG)exp/(AAGGG)exp were not pathogenic, therefore, it is the biallelic expansions of AAGGG that is pathogenic (PMID: 30926972). An additional pathogenic biallelic expansion :RFC1_ACAGG, was seen in was seen in two Asia-Pacific CANVAS families and a Japanese case (PMID: 33103729, 35355059).

Created: 15 Apr 2025, 2:51 p.m. | Last Modified: 15 Apr 2025, 2:51 p.m.

Panel Version: 6.166

RFC1 transcribed from the reverse strand, which means that the repeated sequence is the reverse compliment of the forward strand sequence.

RFC1_AAGGG is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4

RFC1_AAGGG is on https://stripy.org/database

RFC1_AARRG is on DRAGON 4.02.

The coordinates of the sequence repeats shown above were obtained from DRAGON 4.02 and https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
The coordinates of the sequence repeats from https://stripy.org/database were 4:39348424-39348485 (hg38)
The non-pathogenic and pathogenic ranges of the sequence repeats shown above were obtained from: https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r4
And https://stripy.org/database

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature

Created: 15 Apr 2025, 2:20 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, OMIM: 614575

Publications

• 30926972
• 35883251
• 36250766
• 36289003
• 36524104
• 36478048
• 32040566
• 33103729, 35355059