Submissions for variant NM_000033.4(ABCD1):c.293C>G (p.Ser98Trp)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Johns Hopkins Genomics, Johns Hopkins University	RCV002282796	SCV002570394	likely pathogenic	Adrenoleukodystrophy	2022-07-12	criteria provided, single submitter	clinical testing	c.293C>G in ABCD1 has been reported in the literature in association with adrenoleukodystrophy. The variant is absent from a large population dataset and has not been reported in ClinVar, but a different missense change affecting the same residue (p.Ser98Leu) has been classified as pathogenic in ClinVar (Variation ID 458641). Three bioinformatic tools queried predict that this substitution would be deleterious, and the serine residue at this position is evolutionarily conserved across most species assessed. We consider c.293C>G in ABCD1 to be likely pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004731257	SCV005335827	likely pathogenic	ABCD1-related disorder	2024-05-14	no assertion criteria provided	clinical testing	The ABCD1 c.293C>G variant is predicted to result in the amino acid substitution p.Ser98Trp. This variant was reported in two male siblings with childhood onset adrenoleukodystrophy and was inherited from the unaffected mother (Ohi et al. 2000. PubMed ID: 10980309). An alternate substitution at this amino acid position (p.Ser98Leu) has been reported as pathogenic for adrenoleukodystrophy (Feigenbaum et al. 1996. PubMed ID: 8651290; Wiens et al. 2019. PubMed ID: 31074578). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic.