Submissions for variant NM_005219.5(DIAPH1):c.2108dup (p.Pro704fs)

dbSNP: rs771360300

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001919847	SCV002160944	pathogenic	Autosomal dominant nonsyndromic hearing loss 1; Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro704Thrfs*71) in the DIAPH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DIAPH1 are known to be pathogenic (PMID: 24781755, 26463574). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive DIAPH1-related conditions (PMID: 33176815). ClinVar contains an entry for this variant (Variation ID: 1395984). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV002264421	SCV002545356	pathogenic	not provided	2022-05-01	criteria provided, single submitter	clinical testing	DIAPH1: PVS1, PM2, PM3